Arthroscopic-assisted allograft anterior cruciate ligament reconstruction in patients with symptomatic arthrosis

BACKGROUND: Antral motility and the hormone cholecystokinin (CCK) are major determinants of the rate of gastric emptying. The relation between CCK and antral neurons in regulating gastric emptying is uncertain. Benzalkonium chloride (BAC) causes selective lesions in gut myenteric neurons after serosal application. AIM: To develop a model of antral denervation using BAC to enable the study of the relation between CCK and antral neurons in regulating gastric emptying. METHODS: BAC, vehicle or the afferent neurotoxin capsaicin were applied to the serosal surface of the rat antrum or corpus; neurochemical markers of intrinsic and afferent neurons were detected by using immunohistochemistry and radioimmunoassay. Gastric retention of solids was determined after fasting, and emptying of liquids was measured in rats with gastric fistulae. RESULTS: In BAC treated rats radioimmunoassay of tissue extracts revealed a dose related specific loss of gastrin releasing peptide, substance P, and vasoactive intestinal polypeptide immunoreactivities from the treated region, and immunohistochemistry revealed loss of the neuronal marker PGP 9.5 and the afferent neuropeptide calcitonin gene related peptide (CGRP). Adjacent untreated regions were unaffected by BAC, with the exception that CGRP was depleted in both corpus and antrum after antral treatment. After antral BAC treatment fasted rats retained solids for over 48 hours. Moreover, in antrally denervated rats with gastric fistulae, the emptying of saline, acid and peptone was delayed substantially. The CCK dependent inhibition of gastric emptying of peptone was preserved after antral treatment with BAC. CONCLUSIONS: Serosal BAC causes lesions in the innervation of the treated region of the stomach. The innervation of the antrum is essential for normal emptying of both liquids and solids, but the inhibition of gastric emptying produced by CCK is not dependent on antral neurons.     

Diazepam binding inhibitor is a potent cholecystokinin-releasing peptide in the intestine

Pancreatic proteases in the duodenum inhibit the release of cholecystokinin (CCK) and thus exert feedback control of pancreatic exocrine secretion. Exclusion of proteases from the duodenum either by the diversion of bile-pancreatic juice or by the addition of protease inhibitors stimulates exocrine pancreatic secretion. The mechanism by which pancreatic proteases in the duodenum regulate CCK secretion is unknown. In this study, we isolated a trypsin-sensitive peptide that is secreted intraduodenally, releases CCK, and stimulates pancreatic enzyme secretion in rats. This peptide was found to be identical to the porcine diazepam binding inhibitor by peptide sequencing and mass spectrometry analysis. Intraduodenal infusion of 200 ng of synthetic porcine diazepam binding inhibitor1-86 in rats significantly stimulated pancreatic amylase output. Infusion of the CCK antagonist MK-329 completely blocked the diazepam binding inhibitor-stimulated amylase secretion. Similarly, diazepam binding inhibitor33-52 [corrected] also stimulated CCK release and pancreatic secretion in a dose-dependent manner although it was 100 times less potent than the whole peptide. Using a perfusion system containing isolated mucosal cells from the proximal intestine of rats, porcine diazepam binding inhibitor 10(-12) M) dose dependently stimulated CCK secretion. In separate studies, it was demonstrated that luminal secretion of the diazepam binding inhibitor immunoreactivity (7.5 X 10(11) M) could be detected in rat's intestinal washing following the diversion of bile-pancreatic juice. The secretion of this peptide was inhibited by atropine. In conclusion, we have isolated and characterized a CCK-releasing peptide that has a sequence identical to the porcine diazepam binding inhibitor from pig intestinal mucosa and that stimulates CCK release when administered intraduodenally in rat. This peptide may mediate feedback regulation of pancreatic enzyme secretion.     

Regulation of cholecystokinin secretion by peptones and peptidomimetic antibiotics in STC-1 cells

Peptones are potent stimulants of cholecystokinin (CCK) release in rats, both in vivo and ex vivo in a model of isolated vascularly perfused duodeno-jejunum preparation and in vitro in the intestinal CCK-producing cell line STC-1. The underlying mechanisms were here investigated with this cell line. Protein hydrolysates from various origins (meat, casein, soybean, and ovalbumin; 0.5-1%, wt/vol) dose dependently increased CCK release. Cephalosporin antibiotics, which mimic tripeptides, also stimulated the release of CCK over the concentration range 1-20 mM. The study of concentration dependence of cephalosporin uptake indicated a passive diffusion process at either pH 7.4 or pH 6.0, thus arguing against the involvement of a peptide transporter in CCK secretion. After pertussis toxin treatment (200 ng/ml; 5 h), the peptone- and cephalexin-induced CCK secretion was significantly reduced, suggesting the involvement of pertussis toxin-sensitive heterotrimeric G protein(s) in the secretory activity of STC-1 cells. Consistent with this was the identification by Western blot of G(i2)alpha, G(i3)alpha, and G(o)alpha immunoreactivities in STC-1 cell extracts. Additionally, peptones and cephalexin increased the cellular content in inositol phosphates, whereas a mild increase in cAMP content was restricted to peptone-treated cells. Protein kinase A or C inhibition did not modify peptone- or antibiotic drug-evoked CCK release. The extracellular Ca2+ chelator EGTA (500 microM) and the intracellular Ca2+ chelator BAPTA-AM [1,2-bis-(O-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid tetra(acetoxymethyl) ester; 20 microM] abolished the peptone- and antibiotic drug-induced CCK release. Nifedipine and verapamil (10 microM) reduced by about 50% the CCK secretion evoked by these two secretagogues. In conclusion, peptones and some cephalosporins are potent stimulants of CCK release in the STC-1 cell line. The cellular mechanisms involve pertussis toxin-sensitive G protein(s) and are dependent on Ca2+ availability. We suggest that the STC-1 cell line is a useful model to study the molecular basis of peptone-induced CCK secretion.     

Elementary anatomy for the future general practitioner: the arteries

SUT-8701 is a cholecystokinin octapeptide (CCK8) analog and a more lipophilic peptide than CCK8. We previously demonstrated that intra-ventricularly administered CCK8 protected against the degeneration of the cholinergic neurons in the cortex of the nucleus basalis magnocellularis (nbm)-lesioned rat. We determined whether SUT-8701 and CCK8 have the ability to protect against cholinergic degeneration in the cerebral cortex of nbm-lesioned rats. Systemically administered SUT-8701 (0.1-1 micrograms/day/animal, s.c.) preserved choline acetyltransferase activity and K(+)-evoked acetylcholine release in nbm-lesioned rats. SUT-8701 was more potent than CCK8. However, SUT-8701 was much less potent than CCK8 in satiety action. The affinity of SUT-8701 to the cholecystokinin (CCK) receptors assessed by using [125I]-CCK8 was almost the same as that of CCK8 in the mouse cerebral cortex, but was 107 times less than that of CCK8 in guinea pig pancreas. These results suggest that SUT-8701 may be effective in slowing down the degenerative processes in Alzheimer's disease by preserving the integrity of cholinergic neurons in the nucleus basalis.     

Regulation of the action of the novel cholecystokinin-releasing peptide diazepam binding inhibitor by inhibitory hormones and taurocholate

Diazepam binding inhibitor (DBI1-86) has recently been isolated in search for a cholecystokinin (CCK)-releasing peptide in the duodenum that is responsible for the feedback regulation of exocrine pancreatic secretion. Synthetic porcine DBI1-86 stimulates CCK release in vivo and in vitro from isolated intestinal mucosal cells. We postulated that DBI intraduodenally releases CCK in a paracrine fashion and might be the missing link in the feedback regulation of exocrine pancreatic secretion. Somatostatin, peptide YY (PYY) and taurocholate are known to inhibit feedback-stimulated CCK release in the rat. In this study, we investigated the effect of somatostatin, PYY and taurocholate on DBI-stimulated CCK secretion. Dispersed rat intestinal mucosal cells were prepared from the proximal small bowel and continuously perfused. The perfusate was collected and the release of CCK into the medium was measured. DBI1-86 dose-dependently stimulated CCK release, with a maximal effect at 10(-9) M. Somatostatin blocked the DBI-stimulated CCK release. Pretreatment of the cells with pertussis toxin fully reversed the inhibitory effect of somatostatin on DBI-stimulated CCK secretion, suggesting that somatostatin exerts its action by an inhibitory G-protein. In contrast, PYY (10(-6) M) and taurocholate (10(-6) M) did not affect DBI stimulated CCK levels, indicating that they act through different mechanisms to inhibit feedback-stimulated CCK release.     

Structural and functional organization of the enteric nervous system in the stomach

This report summarises some features of the gastric enteric nervous system in the guinea-pig model. Particular attention has been paid to relations between neurochemical properties, electrophysiological and putative function of enteric neurones. (1) Cholinergic and nitrergic neurones form separate neuronal populations. (2) Ascending neurones outnumbered descending ones. (3) Transmitter-phenotype and projection were related: cholinergic neurones were primarily ascending while nitrergic neurones were mainly descending. (4) The neurochemical code, i.e. the transmitter colocalisation, could be related to the function of enteric neurones. Colocalisation of substance P and/or enkephaline in cholinergic neurones was characteristic for ascending excitatory muscle neurones. Descending inhibitory muscle neurones were nitrergic often colocalising the neuropeptides neuropeptide Y (NPY) and vasoactive intestinal peptide (VIP). In the intrinsic innervation of the gastric mucosa NPY/VIP was abundant and colocalised in ascending cholinergic as well as descending nitrergic neurones. (5) The vast majority of ascending and descending interneurones were cholinergic and often colocalised NPY. (6) The majority of descending mucosa and descending inhibitory muscle neurones were tonically-firing neurones. Our results revealed the characteristics of some neural components within the enteric nervous system of the stomach which are involved in modulation of mucosa and muscle functions. It may be concluded that muscle and mucosa functions are under the control of the enteric nervous system which contains distinct populations responsible for motor and secretory activity.     

Mechanism of gastric acid hypersecretion in patients with islet cell tumor without hypergastrinemia: studies in rats

BACKGROUND & AIMS: A nongastrin acid-stimulating peptide (NGASP) has been found in ulcerogenic pancreatic tumor syndrome without hypergastrinemia. The mechanism of gastric acid hypersecretion by NGASP was investigated in rats. METHODS: In vivo, gastric acid secretion and in vitro histamine release from enterochromaffin-like (ECL) cells in responses to tumor extract (TE) and synthetic human gastrin-17 I or pentagastrin (PG) were studied. Whether the 2 secretagogues potentiate each other was determined. RESULTS: TE dose-dependently stimulated histamine release, which was not blocked by a cholecystokinin (CCK)-B receptor antagonist. When TE was incubated with trypsin, the activity was abolished but was not affected by antibody. However, when rats were pretreated with antigastrin serum or CCK-B receptor antagonist, the acid secretion by TE was virtually abolished. The dose response of acid secretion to TE in the rats receiving PG in a threshold dose was significantly greater than that achieved by TE alone. Similarly, the dose response to PG combined with a threshold dose of TE was significantly greater than that produced by PG alone. CONCLUSIONS: NGASP stimulates histamine release from ECL cells, but the release is not mediated via CCK-B/gastrin receptor. NGASP and gastrin may potentiate each other to produce acid hypersecretion in ulcerogenic pancreatic tumor syndrome.     

Neurohormonal mechanisms of cigarette smoke-induced duodenal mucosal bicarbonate secretion in the rat

The effect of cigarette smoke and nicotine on duodenal mucosal bicarbonate secretion (DMBS) was studied in rats. Cigarette smoke but not intravenous nicotine administered acutely to anesthetized rats via a tracheostomy tube stimulated DMBS by 47 +/- 6%. The increase was neurally mediated via atropine-sensitive postganglionic cholinergic neurons. Introduction of cigarette smoke after the infusion of vasoactive intestinal peptide and porcine histidine isoleucine (PHI) also caused a delayed increase in DMBS. However, the magnitude of this increase was similar to that seen in control non-peptide-infused rats. The increase in bicarbonate secretion predominantly involved Brunner's glands. Rats exposed to cigarette smoke for 4 and 8 days before direct instillation of smoke via tracheostomy tube did not show any increase in their DMBS. These studies indicate that in the rat, cigarette smoke increases DMBS, most likely secreted by the Brunner's glands. The increase is neurally mediated via atropine-sensitive postganglionic cholinergic neurons. Gastroenteric neuropeptides do not exert any influence on cigarette smoke-mediated DMBS secretion in the rat. Unlike acute exposure to cigarette smoke, chronic exposure (4 and 8 days) of rats to cigarette smoke abolishes increase in DMBS induced by subsequent exposure to cigarette smoke. This last observation may, in part, may explain the tendency of chronic smokers who have duodenal bulb ulcers to show greater propensity to higher rate of recurrence and protracted healing.     

NMDA receptor activation enhances the release of a cholinergic differentiation peptide (HCNP) from hippocampal neurons in vitro

Hippocampal cholinergic neurostimulating peptide (HCNP) is a novel undecapeptide purified from the hippocampus of young rats. The peptide stimulates cholinergic phenotype development in the rat medial septal nucleus in vitro. Here, we have focused on the mechanism of release of the peptide from the hippocampus, by applying tissue culture techniques. Quantitation of HCNP in the culture supernatant after chemical stimulation was carried out by RIA, and by a combination of HPLC and RIA. We found that the N-methyl-D-aspartate (NMDA) receptor specifically mediates release of the deacetylated form of HCNP from the culture. Our results suggest that during the early development of hippocampal neurons, the peptide is released by NMDA receptor activation, and that it may be involved in mediating the effect of activity-dependent cues on developing septal cholinergic neurons.     

Reduction of neuropeptide Y binding sites in the rat hippocampus after electroconvulsive stimulations

The role of vasoactive intestinal peptide (VIP) was investigated when mucosal stroking and 5-hydroxytryptamine (5-HT) were used to activate neural reflexes that stimulate chloride secretion in the guinea pig colon. Muscle-stripped segments of colon containing intact submucosal ganglia without myenteric ganglia were set up in modified flux chambers in order to record short-circuit current (Isc). Mucosal stroking with a brush for 1 s or a pulse of 5-HT (injection of 15 microliters of 100 microM 5-HT into 1.5 ml of mucosal solution) caused an increase in Isc that was reduced by the VIP antagonist, neurotensin6-11-VIP7-28, in a concentration-dependent manner. The Isc responses to mucosal stroking and a 5-HT pulse were reduced by 53% and 58%, respectively, by 2 microM neurotensin6-11-VIP7-28. The residual Isc response in the presence of neurotensin6-11-VIP7-28 was abolished by atropine. Blockade of 5-HT1P receptors on submucosal afferent neurons decreased Isc responses to stroking or a 5-HT pulse. The residual Isc response after 5-HT1P receptors were blocked was reduced by only 11-14% by neurotensin6-11-VIP7-28. In the presence of blockade of both 5-HT1P and VIP receptors, atropine abolished the Isc response to both stimuli. The observations suggest that the neural circuitry activated by stroking includes at least two independent pathways. One pathway contains VIP neurons which receive inputs directly or indirectly from 5-HT1P receptor-containing afferents. A second pathway involves muscarinic cholinergic transmission that is independent of 5-HT1P and VIP receptor activation.     

Inhibitors of ATP-sensitive potassium channels stimulate intestinal cholecystokinin secretion

Recently, a role for adenosine 5'-triphosphate(ATP)-sensitive potassium channels in the regulation of cholecystokinin (CCK) secretion has been described in STC-1 cells, an intestinal CCK-secreting cell line. To examine whether a similar mechanism might participate in the regulation of hormone secretion from native CCK cells, the effects of two established inhibitors of ATP-sensitive potassium channels (e.g. glucose, disopyramide) were examined on CCK release from dispersed murine intestinal cells. Both glucose and disopyramide were found to stimulate CCK secretion. Furthermore, CCK release induced by glucose was inhibited by the calcium channel blocker diltiazem. It is concluded that, ATP-sensitive potassium channels may play a role in the regulation of intestinal CCK secretion.     

Prolactin release by vasoactive intestinal polypeptide in rats

Synthetic vasoactive intestinal polypeptide (VIP) administered either intraventricularly or iv caused a significant and dose-related increase in plasma PRL levels in urethane-anesthetized rats. The administration of naloxone, an opiate receptor antagonist, significantly blunted the plasma PRL response to VIP. Increases in plasma PRL induced by VIP were also significantly suppressed by L-dopa, a precursor of dopamine, whereas pilocarpine, a cholinergic agonist, diphenhydramine, a histamine antagonist, and cyproheptadine, an antiserotoninergic agent, did not affect the plasma PRL response to VIP. In in vitro experiments, VIP alone did not stimulate PRL release from cultured pituitary cells, but it significantly attenuated the inhibitory action of dopamine, which was not blocked by naloxone. These results suggest that VIP stimulates rat PRL secretion, at least in part, through activation of an opiate receptor in the central nervous system and by blocking the inhibitory action of a dopaminergic mechanism at the pituitary level.     

Cholecystokinin (CCK)-induced stimulation of luteinizing hormone (LH) secretion in adult male rhesus monkeys: examination of the role of CCK in nutritional regulation of LH secretion

Studies were performed with the overall goal of testing the hypothesis that cholecystokinin (CCK), a peptide hormone released from the gastrointestinal tract in response to meal consumption, provides a metabolic signal which modulates LH secretion in response to changes in the body's nutritional intake. In an initial study to document the effects of CCK on LH secretion in adult male rhesus monkeys, sulfated CCK-8 (7 and 15 micrograms/kg) was administered to six monkeys, and blood samples were collected from indwelling venous catheters. The 15-micrograms/kg dose of CCK elicited a rapid release of LH, with peak LH levels of 31.29 +/- 7.19 ng/ml occurring within 5-15 min. To determine the CCK receptor type mediating the effect of CCK on LH secretion, specific CCK type-A (L-364,718) and type-B (L-365,260) receptor antagonists (1 mg/kg) were administered to five monkeys 15 min before CCK administration. The CCK-A antagonist completely blocked LH secretion in response to CCK, whereas the CCK-B antagonist had no effect. To assess whether endogenous CCK, released in response to food intake, stimulates LH secretion, six monkeys were fasted for 1 day and then provided with a normal meal of monkey chow (i.e. a refeed meal) the following day, with either no antagonist, CCK-A antagonist, or CCK-B antagonist administered 30 min before the meal. As previously demonstrated, meal consumption after a brief period of fasting caused a rapid stimulation of pulsatile LH secretion. The refeed meal led to a comparable stimulation of LH secretion regardless of whether monkeys received no antagonist (3.7 +/- 0.44 LH pulses/9 h), CCK-A antagonist (3.33 +/- 0.56 LH pulses/9 h), or CCK-B antagonist (4.0 +/- 0.78 LH pulses/9 h). These results indicate that CCK can stimulate LH secretion in adult male rhesus monkeys, acting via type-A CCK receptors. However, endogenous CCK released in response to meal intake does not appear to be responsible for the meal-induced stimulation of LH secretion that occurs when monkeys are fed a normal meal after a brief period of fasting.     

PACAP stimulates pancreatic exocrine secretion via the vagal cholinergic nerves in sheep

The present study evaluates the possible role of the vagus nerves in mediating the stimulatory effect of PACAP-27, PACAP-38 and VIP on the exocrine pancreas, especially on enzyme secretion which is atropine sensitive in sheep. The animals were equipped with two cannulae into the common bile duct, a duodenal cannula, and a ruminal cannula under anesthesia. The bilateral cervical vagus nerves were coiled with a cooling device. In conscious animals, the peptides were infused intravenously for 10 min at 10 pmol kg(-1)min(-1) in phase II of the duodenal migrating motor complexes and the same peptide infusion was repeated in the reversible cooling blockade of the vagus nerves. Increment in fluid secretion was not significantly altered by the vagal blockade in all the peptide infusions, while increment in bicarbonate ion by only PACAP-27 was inhibited by the vagal blockade. Increments in protein and amylase output decreased significantly to 32.0+/-5.0 and 23.2+/-2.6% in PACAP27, and to 26.1+/-7.7 and 20.8+/-6.4% in PACAP-38 in the vagal blockade, but the increments by VIP did not decrease. These results demonstrate that circulating PACAP stimulates pancreatic enzyme secretion via the vagal cholinergic preganglionic neurons in sheep, suggesting the central action of PACAP.     

Anesthetic experience in congenital arthrogryposis multiplex

Rat pancreatic juice (RPJ) reduced the mean uptake of 57CoB12 bound to rat intrinsic factor (IF) by perfused rat intestinal segments from 30.1 +/- 2.4 (pg 57CoB12 per cm intestine +/- S.E.M.) to 26.7 +/- 2.4 (p less than 0.05). RPJ activated with enterokinase reduced the uptake from 22.8 +/- 2.8 to 16.1 +/- 1.9 (p less than 0.05). RPJ also reduced the uptake from 15.8 +/- 2.3 to 8.3 +/- 2.0 (p less than 0.01) in segments from partially pancreatectomized rats. Rat bile abolished the inhibitory effect of RPJ. The results indicate that in the absence of bile the exocrine pancreatic secretion is capable of inhibiting the intestinal uptake of vitamin B12.     

Feedback regulation of exocrine pancreatic secretion in dogs

Important basic physiological mechanisms of exocrine pancreas secretion were delineated in a canine model. However, dogs have been considered unsuitable for the study of the controversial feedback regulation of exocrine pancreas secretion. The present study reveals a marked modification of pancreas secretion following the intraduodenal instillation of lipase: The postprandial lipase secretion decreases from 2,421 U x 180 min-1 to 1,490 U x 180 min-1, but simultaneously determined cholecystokinin (CCK) concentrations in plasma do not increase under these circumstances. The intraduodenal application of a protease inhibitor (800 mg camostate) significantly stimulates the secretion of the exocrine pancreas in the fasting dog: After 15 min the protein release increased to 133 +/- 30 mg. Intravenous atropine blocks this increase. The plasma concentrations of CCK are not significantly influenced. These results in our canine model show that the secretory activity of the exocrine pancreas depends on the intraduodenal enzyme content. CCK is irrelevant in this context.     

Alterations in the opioid control of LHRH release from hypothalami isolated from aged male rats

Several lines of evidence have suggested that the opioid control of gonadotropin secretion in the male rat is altered with aging. Because neural control of gonadotropins is mediated through luteinizing hormone releasing hormone (LHRH) secreting neurons, we examined the postulated changes in the opioid control of gonadotropins more directly by studying isolated hypothalamic fragments in vitro. Hypothalami from young (75-90 days) and old (18-20 months) males were examined for their ability to release LHRH when incubated with increasing doses of naloxone in a semi-static culture system. Serum concentrations of testosterone and luteinizing hormone (LH) in the donor animals were both significantly lower in old male rats compared with young males. Basal secretion of LHRH was similar in both age groups. Two-way repeated measures ANOVA indicated that naloxone stimulated a significant dose-dependent increase in the release of LHRH into the media. ANOVA also indicated a significant effect of age. We conclude that the changes in the endogenous opioid systems reported to occur with aging are, in fact, linked to differences in LHRH secretion and thus to differences in the dynamic relationship between testosterone and LH in older male rats.     

Clarion cochlear implant: short-term effects on voice parameters

The effect of acetylcholine on the neurointermediate lobe beta-endorphin secretion was studied in the neonatal and in the adult rat in vitro. Acetylcholine stimulated beta-endorphin secretion from the 2-day- and 5-day-old neurointermediate lobe, the effect was dose dependent and more pronounced in the presence of the cholinesterase inhibitor eserine. The 10-day-, the 21-day-old and the adult rat neurointermediate lobes did not respond to acetylcholine, even in the presence of eserine. Basal beta-endorphin secretion was elevated by the D2 receptor antagonist sulpiride, but acetylcholine was without effect in the 10-day-old and in the adult neurointermediate lobe even after dopamine receptor blockade. The beta-endorphin stimulatory response to acetylcholine was diminished by the M1 muscarinic receptor antagonist pirenzepine and blocked by the M3 > M1 antagonist 4-diamino-phenyl-piperidine (4-DAMP). The selective M2 antagonist methoctramine and nicotine had no effect. These data indicate that the neurointermediate lobe beta-endorphin secretion is under special muscarinic cholinergic regulation for a relatively short time after birth. The disappearance of this stimulatory cholinergic effect in later life might be due to changes in the intracellular secretory machinery in the IL and/or to the uncoupling of the cholinergic receptors from the intracellular signal transduction system(s) responsible for the stimulated secretion in the rat melanotrope cells.     

Rectal sexual trauma including foreign bodies

We used a potent and specific monoclonal antibody to somatostatin to test the physiologic inhibitory role of the tetradecapeptide somatostatin on pancreatic secretion. Somatostatin immunoneutralization increased both the total amylase and volume of pancreatic secretion. Cholecystokinin-A receptor antagonism abolished the stimulatory effect of somatostatin immunoneutralization. We conclude that somatostatin tonically inhibits, pancreatic secretion in fasted rats via inhibition of the release or action of cholecystokinin. Furthermore, the source of these peptides is likely islet delta cells and intrapancreatic neurons, respectively.