Adrenergic innervation of the urinary bladder body in the cat with special reference to structure of the detrusor muscle: an immunohistochemical study of noradrenaline and its synthesizing enzymes

The distribution of adrenergic nerves in the body detrusor muscle of the cat urinary bladder was studied by means of the immunohistochemical identification of noradrenaline (NA) and the NA synthesizing enzymes tyrosine hydroxylase, aromatic L-aminoacid decarboxylase and dopamine beta-hydroxylase. We identified the basic structural organization of the detrusor muscle, which had previously been described as lacking discernible layers. In the lateral wall, both outer longitudinal and inner circular muscle bundles were present, the latter extending in both anterior and posterior directions. The posteriorly running bundles came to lie on the outside of the posterior wall where they enabled recognition of inner longitudinal muscle bundles. Those running anteriorly were dispersed to enter the longitudinal bundles in the anterior wall. NA-immunoreactive nerve fibers in the detrusor muscle of the bladder were found to be similar to those immunoreactive for NA synthesizing enzymes in both distribution and density. In the upper and middle bladder body--including the dome (apex)--immunoreactive nerve fibers were always more abundant in the outer part of the detrusor muscle than in the inner part, regardless of the course of muscle bundles. Even in individual muscle bundles running from the inside to the outer surface, the outer part was more richly innervated by immunoreactive fibers than the inner part. In the bladder dome, a moderate number of immunoreactive nerve fibers preferentially innervated the outer part of the muscle layer. In the lower bladder body, these nerve fibers increased in density in the inner part of the detrusor muscle. There was no sexual difference in density or distribution of nerve fibers. NA- and NA synthesizing enzyme-immunoreactive nerve fibers were markedly decreased in number after 6-hydroxydopamine treatment. No dopamine- or phenylethanolamine-N-methyltransferase-immunoreactive nerve fibers were present in the bladder. The findings of this study indicate that the cat bladder musculature includes longitudinal and circular muscle bundles, both of which are extensively innervated by adrenergic nerves, particularly in the outer part of the bladder.     

On the intrinsic innervation of normal rat liver. Histochemical and scanning electron microscopical studies

With the Bodian method stained fibers were observed in the lobules of the rat liver and with the modified Karnovsky and Roots thiocholine method cholinesterase (presumably acetylcholinesterase (AChE))-positive nerve fibers were found in a pattern similar to that of the Bodian-stained fibers. The AChE-positive nerve fibers form a network in the liver lobules in close relation to hepatocytes and sinusoids. Fluorescent varicose nerve fibers demonstrated by the glyoxylic acid and Falck-Hillarp fluorescence methods were found only in the interlobular spaces associated with vessels. As no overlapping of distribution patterns of AChE-positive nerve fibers and fluorescent nerve fibers occurs, the AChE activity of the nerves of the liver lobules probably reflects the associated presence of acetylcholine in the nerve fibers. In consequence we suggest that nerves of the liver lobules belong to the autonomic parasympathetic nervous system. SEM of liver tissue revealed light cords apparently situated in smooth-surfaced channels between adjacent hepatocytes and in the space of Disse, where fibers also cross sinusoids. We tentatively suggest that the cords of the SEM represent the AChE-positive nerve fibers of our LM observations.     

Transitional carcinomas of the urinary tract: synchronous and metachronous lesions

OBJECTIVE: The urothelium is a pseudostratified cylindrical epithelium that lines the calices, renal pelvis, urethers, bladder, part of the urethra and part of the prostate ducts. Transitional cell carcinoma (TCC) is a malignant neoplasia that can appear in any site where urothelium is present, being the bladder the most frequently affected organ. We performed an analysis of our experience and conducted a literature-based metanalysis to evaluate the coexistence of tumoral lesions at different locations in the urinary tract. MATERIAL AND METHODS: Between 1983 and 1993, 397 patients with TCC lesions involving the upper urinary tract (UUT), bladder, urethra or prostate, were diagnosed and treated. Coexistence, either synchronic or metachronic, of several lesions in different sites of the urinary tract was considered as a multiple tumor. RESULTS: Overall, 440 tumors were diagnosed in 397 patients. A single lesion appeared in 360 patients, while 37 presented multiple locations with a total of 79 tumors. The lesions were located at the following levels: 17 renal, 21 uretheral, 372 vesical, 13 in the urethra and 17 in the prostate ducts. According to the location, the frequency of single lesions was: UUT 58%, bladder 91%, urethra 8% and prostate ducts 35%. Synchronic UUT and intravesical tract tumors develops in 1% and 4% of patients with bladder TCC, respectively. Two percent of vesical tumors showed metachronic relationship with UUT tumors and the same rate was seen for intravesical lesions. CONCLUSIONS: Urothelial UUT tumors have a typical nosologic entity with specific features. Their coexistence with vesical tumors is frequent. When tumors of the bladder occur after a UUT tumor the interval of highest incidence between diagnoses is 2-3 years, and there are no histological risk factors among them for prognosis. Transitional cell prostatic urethral tumors are most often secondary to histologically similar, poor prognosis, bladder tumors, and usually synchronic.     

A quantitative assessment of innervation in the conduction system of the calf heart

BACKGROUND: The aim of the present investigation was to determine the relative distribution of autonomic and sensory nerves in the cardiac conduction tissues of calves. METHODS: A quantitative immunohistochemical and histochemical technique was adopted. RESULTS: Immunoreactivity to the general neuronal marker protein gene product 9.5 (PGP 9.5) demonstrated that all regions of the conduction system possessed a higher relative density of total nerves when compared with the surrounding myocardial tissues. Unlike myocardial innervation, the conduction system did not display an atrial-to-ventricular gradient in nerve density. PGP 9.5-immunoreactive nerve trunks and varicose nerve fibres were more numerous in the transitional atrioventricular node and the penetrating atrioventricular bundle than in either the sinus node, compact atrioventricular node, or bundle branches. The Purkinje network of the ventricular conduction tissues possessed a rich supply of PGP 9.5-immunoreactive nerve trunks and varicose nerve fibres. Acetylcholinesterase (AChE)-positive nerves were the main subtype identified in the sinus and atrioventricular nodes and in the ventricular conduction tissues, representing 50-80% of the area occupied by PGP 9.5-immunoreactive nerves. The compact atrioventricular node possessed AChE-positive and tyrosine hydroxylase (TH)-immunoreactive nerves in similar proportions (45%), although, in general, TH-immunoreactive nerves had a lower relative nerve density than AChE-positive nerves. Neuropeptide Y (NPY)-immunoreactive nerves represented the main peptide-containing subpopulation and occurred throughout the conduction system, displaying a similar pattern of distribution and relative density to those demonstrating TH immunoreactivity. Nerve fibres immunoreactive for somatostatin, vasoactive intestinal polypeptide, substance P, and calcitonin gene-related peptide formed relatively minor subpopulations. CONCLUSIONS: The general innervation of the bovine conduction tissues exhibits significant regional variation. Throughout all regions of the conduction system, AChE-positive nerve represented the dominant subtype when compared with TH- and NPY-immunoreactive nerves. The distribution and relative density of nerve subtypes in the tissues of the bovine conduction system are similar to those observed in man, whereas differences were observed in other regions, such as the atrioventricular bundle and bundle branches. This finding must be considered by those making interspecies comparisons.     

Plastic repair of the urinary bladder

Clinical observations of 76 patients in whom an artifical urinary bladder was constructed from the rectum are presented. 52 patients were operated upon for cancer of the urinary bladder, total papillomatosis, a metastasis of uterine cancer in the bladder, cancer of the sigmoid with the urinary bladder involvement, sarcoma and cancer of the prostate with the bladder involvement. 17 patients were operated upon for extrophy, 7 -- for cancer of the urethra. An isolation of the rectum is followed by ligation of the upper rectal and vein. Fifteen patients died postoperatively due to peritonitis (6), ascending infection of the urinary tract (4), postoperative shock (I), phlegmon of the minor pelvis (I). In late postoperative period an artificial urinary bladder provides for reservoir and excretory functions.     

Foreign bodies of the bladder and urethra. Apropos of 2 cases

The bladder and urethra can be the site of various types of foreign bodies. The authors report two cases of low urinary tract foreign bodies. The first case concerned a young man with psychiatric disorders who introduced a condom into his bladder and the second case was an elderly patient with a history of self-dilation who introduced a safety pin into his urethra. In the light of these two cases, the authors review the diagnostic features and management of bladder and urethral foreign bodies.     

Colocalization of nitric oxide synthase and some neurotransmitters in the intramural ganglia of the guinea pig urinary bladder

The distribution of nitrergic neurons was investigated by using nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d) histochemistry and nitric oxide synthase (NOS) immunohistochemistry in wholemount preparations of the urinary bladder in guinea pigs. Both NADPH-d+ and NOS+ neurons were located predominantly in the bladder base. Double staining showed that 70.9% of the NADPH-d+ neurons coexpressed NOS. Acetylcholinesterase histochemistry revealed that a majority of the intramural neurons were reactive, and about half of them (51.4%) were double labelled for NOS. Tyrosine hydroxylase-positive neurons were also distributed mainly in the bladder base but in a neuronal population that was separate from the preponderant NADPH-d+ neurons. Vasoactive intestinal polypeptide immunoreactivity was also detected in the some of intramural ganglion cells, in which 21.3% of them coexpressed NADPH-d. Calcitonin gene-related peptide and substance P immunoreactivities were confined to nerve fibers, often in close association with NADPH-d+ cells or extended along the blood vessels. These results have demonstrated the colocalization of NADPH-d and NOS in the majority of intramural ganglion cells. Many of the nitrergic neurons are apparently cholinergic, indicating that they are parasympathetic postganglionic neurons, and this underscores NO as the major neuromodulator in the parasympathetic nerves in the bladder walls. The localization of vasoactive intestinal polypeptide in nitrergic neurons suggests that the peptide may complement NO for regulation of micturition reflex. The close relationship of NADPH-d-reactive intramural neurons with calcitonin gene-related peptide and substance P fibers, most probably derived from dorsal root ganglion cells, suggests that NO released from the local neurons may exert its influence on the sensory neural pathways in the urinary bladder.     

Cytokine repertoire of epithelial cells lining the human urinary tract

PURPOSE: To examine the cytokine profile of epithelial cells lining the human urinary tract with the aim of differentiating between the constitutive and disease-related cytokine production in these tissues. MATERIALS AND METHODS: Sections from the renal pelvis, ureter, bladder or urethra were obtained from 22 patients undergoing urinary tract surgery and were stained with monoclonal antibodies to interleukin(IL)-1beta, IL-4, IL-6, IL-8, interferon gamma (IFNgamma) and transforming growth factor beta (TGFbeta). Sections were classified according to the presence or absence of disease in the tissue. RESULTS: Epithelial cells lining the renal pelvis, ureter, bladder or urethra all stained for IL-8 and TGFbeta (100%) in disease-free tissues and sections with cancer or interstitial cystitis (IC). In contrast, staining for IL-1beta, IL-4, IL-6 and IFNgamma varied with the disease state of the patient. Epithelial IL-1beta staining was absent (0%) in sections from healthy bladder, but positive in tissues with IC or cancer-associated pathology (50 to 100%). IL-6 staining was detected in the epithelial layer of several patients with IC or cancer related pathology, but only in cells with non-epithelial morphology and not in disease-free tissues. IFNgamma and IL-4 staining were only observed in patients with IC and only in cells with non-epithelial morphology. CONCLUSIONS: The results show that epithelial cells from all parts of the urinary tract constitutively produce IL-8 and TGFbeta and suggest that the production of other cytokines varies with the disease of the patient. Constitutive cytokine production provides the basis for a rapid host response, in the defense against mucosal attack by microbes or toxic agents.     

Anatomical anterior exenteration with urethral and vaginal preservation: illustrated surgical method

PURPOSE: We describe in detail a method for urethral and vaginal preservation in women considering orthotopic urinary tract reconstruction after bladder removal. MATERIALS AND METHODS: We retrospectively reviewed the pathological reports of patients treated with anterior exenteration at our hospital between 1984 and 1997 for specific evidence of urethral, vaginal, cervical or uterine involvement by the primary bladder tumor. Based on our findings we describe our approach to anterior exenteration in 6 patients. RESULTS: A total of 46 patients were treated at our center with en bloc anterior exenteration and pelvic lymphadenectomy for primary bladder cancer between 1984 and 1997. In 7 patients (15%) pathological review of the surgical specimen documented urethral involvement by the primary tumor. In 1 patient (2%) microscopic evidence of tumor was identified in the cervix and 1 (2%) had tumor extension to the vagina documented in the final pathology report. CONCLUSIONS: The observed rates of vaginal and urethral involvement agree with those reported by others, and suggest that in the majority of women treated with anterior exenteration sacrifice of the urethra and vagina is usually not necessary from an oncological perspective. This procedure is particularly appropriate in women concerned with postoperative sexual function and those considering orthotopic reconstruction of the lower urinary tract after exenterative bladder cancer surgery.     

Effects of hypoxemia on the electroretinogram in diabetics

The localization of the neural cell adhesion molecule L1 in the male urogenital tract (including seminal vesicles and prostate) of the mouse and bull was investigated using immunocytochemical and immunochemical methods in order to better understand the function of this glycoprotein in non-neural tissues. L1 antibodies labeled non-myelinated nerves in all portions of the urogenital tract investigated. However, L1 immunoreactivity was also found between epithelial cells of several regions of the urogenital system including epididymal tail, deferent duct, ejaculatory duct and seminal vesicles. Some L1 immunoreactivity was also demonstrated between epithelial cells of murine urinary bladder and urethra. The specificity of the immunoreaction was verified by western blots. There was no correlation between L1 expression and proliferating activity as revealed by double immunocytochemistry using various markers of cell proliferation. This unexpected expression of L1 in nonneural tissues is mainly restricted to non-proliferating epithelia of those portions of the urogenital tract that are derived from the Wolffian duct. It is suggested that L1 in these epithelia could enhance the mechanical resistance and reduce transepithelial permeability.     

Neuro-histochemical study of the adrenal gland of Rattus rattus rufescens (Indian black rat) as revealed by cholinesterase technique

The present investigation was undertaken to study the innervation and acetylcholinesterase (AChE) distribution in the adrenal gland of Rattus rattus rufescens (Indian black rat) by cholinesterase technique. The percentage of myelinated nerves in the cortical zone (cortex) and medulla zone was high. AChE-positive and multipolar ganglia on the outer medulla region, and the ganglia and nerve cells, arranged in chain-like fashion in the chromaffin tissue, were recorded. AChE activity was marked in the cortical zone (in the form of spots) and in the medulla zone (in the form of white and black grains).     

Membrano-bulbo-urethral junction stenosis. Posterior urethra obstruction due to extreme caliber disproportion in the male urethra

OBJECTIVE: Based on 4 cases of infravesical obstruction due to extreme caliber disproportion between the posterior urethra and the penile urethra, a pathophysiological mechanism for this dynamic obstruction is given and endoscopic treatment is described. SUBJECTS: Four cases of membrano-bulbo-urethral junction (MBUJ) stenosis, seen between September 1995 and April 1996, are described. Two boys had previous successful valve resection but still showed extreme ballooning of the posterior urethra. The other 2 boys showed bladder instability on urodynamics and the male variant of the spinning top urethra on voiding cystourethrography (VCUG). RESULTS: All cases were successfully treated by endoscopic incision at the 12 o'clock position of the kink between the posterior and the penile urethra which is seen when the full bladder is expressed. Disproportion in the posterior urethra, seen on VCUG, together with bad urinary flow measured on uroflowmetry raise the suspicion of MBUJ stenosis. CONCLUSION: Although rarely seen, extreme caliber disproportion in the male urethra can cause obstruction. Ballooning of the posterior urethra, caused by urethral valves, bladder instability resisted by voluntary sphincter contraction or congenital posterior urethral dilatation, creates an obstructive kink in the urethra comparable to some obstructions in ureteropelvic junction stenosis. If suspicion of such a form of obstruction arises, cystoscopy during pressure on the full bladder is mandatory in order to see the obstruction, descending as a membrane from the vault of the urethra.     

Immunological comparison of native streptokinase with streptokinase fragments

Three female patients with complete urinary incontinence owing to congenital absence of the urethra associated with complex congenital anomalies involving the caudal end of the urogenital sinus are reported. A sphincteric tube constructed from a flap of the anterior bladder wall was positioned in place of the missing urethra. Abundance of circularly oriented fibers in this neourethra provided sphincteric function sufficient to maintain continence and eliminate the need for urinary diversion. Details of the congenital anomalies and reconstructive techniques are discussed.     

Correlation of the cystoscopic appearance and functional integrity of the female urethral sphincteric mechanism

OBJECTIVES: Urologists in the past, and many today, rely on the cystoscopic appearance of the female urethra as a guide to its functional integrity. To assess the accuracy of this approach better, we compared the cystoscopic appearance of the bladder neck and proximal urethra to the functional integrity of this mechanism during videourodynamic studies. METHODS: One hundred consecutive videourodynamic studies were reviewed on female patients with more complex types of urinary incontinence. Reports of their cystoscopic examinations were reviewed and results compared. RESULTS: Significant dysfunction of the intrinsic mechanism was noted in 36% of the patients (26% moderate dysfunction and 10% severe dysfunction) on video studies. Cystoscopy underestimated these deficits 74% and 44% of the time, respectively, in the moderate and severe dysfunction groups. CONCLUSIONS: We conclude that the cystoscopic appearance of the bladder neck proximal urethra cannot predict the functional integrity of this mechanism.     

Failure to differentiate Cryptosporidium parvum from C. meleagridis based on PCR amplification of eight DNA sequences

PURPOSE: Little is known about the developmental effects of high urinary diversion and bladder defunctionalization in infancy. Although clinical experience shows that a poorly functional bladder may result from urinary diversion in infancy, the mechanisms of change and specific bladder wall alterations have not been well characterized. We hypothesized that cyclic filling and emptying are necessary for normal bladder development. To investigate this important question we created a new animal model. MATERIALS AND METHODS: We designed a new method of hemibladder urinary diversion in 3-week-old New Zealand white rabbits. After vertical midline bladder division half of the bladder was formed into a functional reservoir, which remained in continuity with the ipsilateral ureter and urethra. The other bladder half was defunctionalized and isolated from the urine flow by ureteral ligation. Diversion was created for 3, 7, 14 and 28 days. Urodynamic evaluation was done in the functionalized hemibladders and age matched normal rabbit bladders to test the validity of the functionalized hemibladder as an internal control. Functional and defunctionalized hemibladders as well as age matched, nonoperated normal rabbit bladders were weighed, sectioned and stained to demonstrate muscle and connective tissue components. RESULTS: In 22 of the 27 healthy rabbits (81%) good quality diverted and functional bladder specimens were obtained after diversion. Defunctionalized hemibladders grew more slowly than functionalized bladders and normal age matched control bladders. Histological staining of the bladder wall demonstrated increased connective tissue between the muscle bundles within the diverted specimens than in functional bladders. CONCLUSIONS: Our successful model of urinary diversion may be used to study the developmental and histological effects of urinary diversion in the young bladder. Bladder growth and histological appearance are altered when the stimulus of cyclic filling and emptying is removed. Further studies using this model are warranted to define fully bladder changes that result from diversion and investigate the mechanism of the observed changes.     

Greater disorderliness of ACTH and cortisol release accompanies pituitary-dependent Cushing''s disease

BACKGROUND: We examined the mechanism of urinary bladder motility return after bladder areflexia induced by interruption of the sacral parasympathetic outflow to the urinary bladder following damage to the sacral cord or pelvic nerves in the rat. METHODS: The L6 and S1 nerve bundles were resected near the vertebrae, and bilateral pelvic nerve resections (PNR) performed. Spinal cord injury (SCI) was performed by means of a legion generator at the T12 vertebra. Thirty days after PNR and SCI, cystometrograms were recorded under anesthesia. RESULTS: In all rats subjected to PNR or SCI, overflow incontinence continued, yet some rats subjected to SCI recovered within 2 weeks after the operation. Cystometrograms showed that repetitive bladder contractions appeared in rats subjected to SCI irrespective of hypogastric nerve (HGN) innervation, while bladder contractions did not appear in rats subjected to PNR. Electrical stimulation of the HGN induced higher bladder pressure elevation in rats who underwent PNR than in rats subjected to SCI. CONCLUSIONS: These results suggest that the generation of repetitive bladder contractions induced by bladder distention after bladder areflexia requires the presence of intact pelvic nerves that transmit sacral cord-originating excitatory information to the bladder. However, the HGN system and functioning pelvic nerve ganglia are not involved in this process. Also, the connection from the preganglionic HGN to the postganglionic parasympathetic nerves in the pelvic plexus did not form after PNR.     

Ultrasonography of urinary bladder disorders

Ultrasonography is often recommended as the first diagnostic imaging modality in patients with hematuria or dysuria. It can provide information relative to the capacity of the urinary bladder, changes in bladder outline, changes in wall thickness, identification of mural and luminal masses, and identification of extrinsic lesions that may displace the bladder wall causing changes in its shape. Ultrasonography allows an evaluation of the entire urinary tract (except distal urethra) in both female and male dogs as well as the sublumbar region for lymphadenopathy.     

A novel in vitro bladder pelvic nerve afferent model in the rat

OBJECTIVE: To develop an in vitro model to allow electrophysiological recordings from pelvic nerve afferents of the urinary bladder in the rat and to ascertain the stability and reproducibility of the model with time. MATERIALS AND METHODS: Six male Wistar rats (body weight approximately 100 g) were used in the study. The bladder (complete with accessory organs of prostate and seminal vesicles), urethra and penis, together with the attached pelvic nerve and L6/S1 nerve trunk, were removed intact and placed in a specially designed recording chamber containing oxygenated Krebs solution maintained at 30 degrees C. The bladder was catheterized urethrally and attached to a continuous-infusion pump and a pressure transducer. The L6/S1 nerve trunk was placed across a silicone-gel wall into a separate chamber containing liquid paraffin, in which multiunit recordings from pelvic nerve afferents originating from the bladder were made. The afferent nerve activities in response to repeated bladder distension with saline, at 0.04 mL/min for 8 min over 3 h, were compared using the paired t-test to assess the reproducibility of the model. Conduction velocity studies were also carried out to ascertain the proportion of C- and A delta-fibres in the multiunit recordings. RESULTS: Repeated bladder distension with saline over 3 h produced consistent and reproducible afferent nerve responses, signifying that the afferent nerves recorded in this study neither sensitize nor desensitize over time. This is an essential prerequisite when using this model to study the effects of pharmacological manipulation of the bladder on its afferent nerve response. Conduction velocity studies showed that approximately 30% of the afferent fibres recorded from were C-fibres with the remaining being A delta-fibres. CONCLUSIONS: An in vitro bladder pelvic nerve afferent model for the rat was developed successfully; it is stable and produces reproducible results with repeated bladder distension over at least 3 h.     

Current aspects in the diagnosis and treatment of chronic cystitis in women

Chronic cystitis (CC) in females is annually encountered now in 15,000-20,000 per 1,000,000. Etiological and pathogenetic factors in CC are closely related. Bacteriologically, CC is represented primarily by Enterobacter. The infection, as a rule, ascends the lower urinary tracts. The contributing factors are: weak local antibacterial mechanisms of the urogenital system, anatomical variants and anomalies of the urethra and introitus, sexual activity, impaired urodynamics of the lower urinary tracts. The diagnosis of chronic inflammation of the bladder is made mainly endoscopically, with obligatory endovesical multifocal biopsy of the bladder followed by histological examination. The treatment of CC includes antibacterial, general and local antiinflammatory therapy, measures to normalize urodynamics of the lower urinary tracts, correction of hygienic and sexual factors, immunostimulation. 16 nonresponders to conservative treatment of interstitial cystitis with progressive contraction of the bladder were subjected to supratrigonal or subtotal resection of the bladder with one-stage ileocystoplasty.     

Morphology and histochemistry of the rabbit pancreatic innervation

Stimulation of extrinsic nerves markedly alters pancreatic endocrine and exocrine secretion, yet little is known of the neurochemical organization and physiologic roles of specific neural pathways within the pancreas. Here we report histochemical staining for acetylcholinesterase (AChE), NADPH-diaphorase (NADPH-d), nitric oxide synthase (NOS), and several neuropeptides to identify the neurotransmitter content of rabbit pancreatic nerves. An extensive network of AChE-positive nerve fibers was found throughout the islets, acini, ducts, ganglia, and blood vessels. All pancreatic neurons were AChE positive, two thirds were NADPH-d positive, and many were NOS positive. Ganglia in the head/neck region were connected to the duodenal myenteric plexus by AChE- and NADPH-d-positive fibers, and NADPH-d-positive pancreatic neurons appeared to send processes toward both the duodenum and pancreas. Many pancreatic neurons were vasoactive intestinal peptide (VIP) positive, and VIP nerve terminals were abundant in ganglia, acini, islets, and ducts. Pituitary adenylate cyclase-activating peptide (PACAP-38)-positive fibers also were observed within acini and passing through ganglia. Substance P (SP)-, calcitonin gene-related peptide (CGRP)-, and dopamine beta-hydroxylase (DBH)-positive fibers were abundant along blood vessels and ducts, and varicose fibers were observed in pancreatic ganglia. Fine galanin-positive fibers were also occasionally observed running with blood vessels and through ganglia. Thus the rabbit pancreas receives a dense, diverse innervation by cholinergic, adrenergic, and peptidergic nerves and cholinergic pancreatic neurons, most also containing VIP or NOS or both, appear to innervate both endocrine and exocrine tissue, and may mediate local communication between the duodenum and pancreas.