Gastrin-producing endocrine cells: a novel source of histamine in the rat stomach

Gastrin and histamine both potently stimulate secretion of acid into the gastric lumen. How these agents interact and how their release is controlled is poorly understood. Therefore, we decided to look for histamine in the antral portion of the rat stomach where the gastrin-producing G cells are located. We used immunocytochemical methods to visualize histamine, histidine decarboxylase (HDC, the enzyme that converts histidine to histamine), and the type 1 vesicular monoamine transporter (VMAT1, the protein responsible for moving histamine into vesicles for storage and release). We were surprised to find that histamine, HDC, and VMAT1 were all present in G cells. Our results suggest that G cells synthesize and secrete gastrin and histamine. Whether histamine acts in concert with gastrin to stimulate acid secretion, or functions as an autocrine inhibitor of gastrin release remains to be seen.     

Effects of histamine on rat isolated atria

The effects of histamine were studied in atria obtained from untreated and reserpine-pretreated rats. At high doses, histamine caused a positive chronotropic response that was not antagonized by either promethazine or cimetidine. In the presence of propranolol or in atria from reserpine-pretreated rats histamine caused an atropine-sensitive negative chronotropic response. Large doses of histamine also caused a positive inotropic response in left atria that were antagonized by the beta adrenoceptor antagonist propranolol. Reserpine pretreatment abolished the inotropic response of histamine in the rat heart. The results indicate that in large doses histamine causes an indirect stimulation of beta adrenoceptors (right and left atrium) by releasing endogenous noradrenaline and of muscarinic receptors (right atrium) by releasing acetylcholine.     

Effects of reserpine on tissue calcium and contractility of rat and rabbit aorta

Possible effects of reserpine on disposition and availability of tissue calcium, stores for excitation-contraction coupling in isolated rat and rabbit aortae were examined. Contral 40Ca uptake, 45Ca washout, and contraction in Ca2+-free medium (Ca2+-free PSS) indicate species differences in binding or disposition, apparent functional importance, and differential use of tissue calcium by adrenaline (Epi) and high K+. Rat aortae, normally refractory to Epi or high K+ after 7 min in Ca2+-free PSS, can gain labile calcium after brief exposure to Ca2+-rich PSS which supports short-lived responses to high K+ in Ca2+-free PSS. Rabbit aortae contain calcium stores which may sustain either Epi or high-K+ responses as well as more tightly held (or sequestered) stores released by Epi for contraction. After reserpine, decreased 45Ca uptake in a kinetically defined "fast" compartment likely to include membrane calcium could enhance availability of bound tissue as well as free Ca2+ in both species. Enhanced Epi response in Ca2+-free PSS is evidence of the former. Results suggest that increased availability of bound and possibly free calcium contribute to reserpine-induced supersensitivity, but supporting evidence will be required from tissue behavior after less rigorous treatment.     

Effects of riboflavin deficiency on the ultrastructure of rat sciatic nerve fibers

Ultrastructural studies indicate that riboflavin deficiency induced by either dietary restrictions alone or with the addition of the antagonist galactoflavin severely affects the structural integrity of myelin lamellae. The degenerative process induced by riboflavin deficiency is time dependent. Nonmyelinated nerve fibers are not affected ultrastructurally by the deficiency. Cellular organelles of both myelinated and nonmyelinated nerve fibers remain intact and presumably functional.     

The ultrastructure of endocrine cells in the corpus of the stomach of human fetuses

The ultrastructural development of endocrine cells from the corpus of fetal human stomachs is described. Samples were taken from fetuses ranging in fertilization age from 6-8 to 22 weeks. The identifying features used for the classification of the various types of endocrine cells were their basal locations in the epithelium, the presence and morphology of their characteristic granules and the sizes of the mitochondria. Five types of endocrine cells with specific granules were found:D, EC, ECL, AL and D1. The type and number of endocrine cells increased as development proceeded. The endocrine cells were confined to the epithelium, they did not reach the lumen and they appeared to develop in situ. The D, EC and ECL cells were the most numerous. The fetal endocrine cells resembled morphologically those found in the stomachs of various adult animals. The EC, ECL and D1 cells contained small slender mitochondria with few cristae. Intramitochondrial granules were absent in all the cell types. Agranular electron-lucent cells with small mitochondria were considered to be immature endocine cells. The advanced stage of differentiation observed in these cells suggest that they may be capable of producing and storing biogenic amines and polypeptide hormones. Their possible involvement in the synthesis of serotonin, enteroglucagon and intrinsic factor is discussed.     

Gastric ECL-cell hyperplasia produces enhanced basal and stimulated gastric acid output but not gastric erosion formation in the rat

Cervical involvement is one of the major prognostic factors in carcinoma of the endometrium confined to the uterus. The purpose of this study was to determine whether intrauterine ultrasound with a high-frequency miniature probe can depict the degree of cervical involvement of the disease. Thirty-two women with endometrial carcinoma underwent preoperative transvaginal and intrauterine sonography. By both scans, the degree of cervical involvement was prospectively evaluated. Sonograms were compared with the findings from histologic examination. Intrauterine sonography was completed in 30 of the 32 patients. In these 30 patients, the degree of cervical involvement (none, endocervical gland, or cervical stroma) based on transvaginal scan was correct in 23 cases (77%), and that based on intrauterine scan was correct in 26 cases (87%). Three tumors with endocervical glandular involvement were correctly diagnosed by intrauterine sonography, whereas they were incorrectly diagnosed by transvaginal scan. The specificity and positive predictive value of intrauterine sonography for the assessment of the presence of cervical stromal invasion are 100% (26/26 and 3/3, respectively). Although this study is preliminary, our experience with intrauterine sonography shows that it has potential for assessing cervical stromal invasion in endometrial carcinoma.     

Influences of Mg++ and reserpine on calcium fluxes and sensitivity of the rat aorta

Rat aorta became supersensitive and subsensitive to noradrenaline (NA), respectively, in Mg++-free and 3.6 mM Mg++ media reserpine treatment reduced the sensitivity in normal or high (3.6 mM) Mg++ media but had no effect in Mg++-free medium. Incubation of aortae in Mg++-free medium enchanced 45Ca++ uptake and efflux in rat aorta, whereas, it reduced 45Ca++ efflux without a change in 45Ca++ uptake by rabbit aorta. Reserpine pretreatment enhanced 45Ca++ efflux from rat aorta without a changed in 45Ca++ uptake in normal Mg++-free medium. Unlike in rat aorta, reserpine enhanced 45Ca++ uptake by and reduced efflux from rabbit aorta in Mg++-free medium but not in normal medium. These results suggest that the failure of reserpine to induce supersensitivity in rat aorta to NA may be due to poor capacity of the muscle to retain Ca++ and probably also due to an enhanced antagonism of Mg++ on Ca++ movements.     

The effect of beta andrenoceptor stimulation of canine stomach on pentagastrin-stimulated histamine release

The effect of beta adrenergic agonist isoproterenol, infused directly into the gastrosplenic artery in anesthetized mixed-breed dogs, on pentagastrin-stimulated gastric histamine release was examined to clarify the potential mechanisms by which beta adrenoceptor stimulation results in gastric acid inhibition. Two doses of isoproterenol (3 and 10 ng/kg/min) were infused with pentagastrin; histamine and n(tau)-methyl-histamine concentrations were measured in arterial and gastric venous samples, and their gastric secretory rates were calculated. Both doses of isoproterenol decreased histamine-secretory rate to pentagastrin from a peak of 234 +/- 51.5 ng/min with vehicle to 17.7 +/- 4.2 ng/min with the 3 ng/kg/min dose of isoproterenol and to 8.6 +/- 2.9 ng/min with the 10 nk/kg/min dose of isoproterenol. The change in N(tau)-methyl-histamine-secretory rate paralleled the histamine-secretory rate. Concomitantly with the histamine-secretory rate, the effect of beta adrenoceptor agonist on gastric somatostatin secretion was also examined. The lower dose of isoproterenol stimulated somatostatin-secretory rate from 4.0 +/- 1.8 to 31.8 +/- 10.3 ng/min, and the higher dose of isoproterenol increased somatostatin-secretory rate from 6.0 +/- 3.1 to 61.5 +/- 21.5 ng/min, whereas isoproterenol potentiated pentagastrin-stimulated gastric somatostatin release. These data demonstrate that isoproterenol is a potent inhibitor of pentagastrin-stimulated gastric histamine release, and the mechanism may be related to the concomitant somatostatin release. Thus, the most likely mechanism by which beta adrenoceptor stimulation results in inhibition of gastric acid secretion is through down-regulation of gastric histamine release.     

Effects of ischaemia-reperfusion and cyclosporin-A on cardiac muscle ultrastructure

The present study investigates the effects on the cardiac muscle cell of two of the determining factors for the success of organ transplant; ischaemia-perfusion and immunosuppressive treatment with cyclosporin-A (CsA). To this end an abdominal, heterotopic heart transplant model in singenic Sprague-Dawley rats was employed. Three study groups were established: Group I (control, n = 15) animals undergoing heart transplant without treatment; Group II (n = 15) animals undergoing heart transplant and subjected to a daily dose of CsA in a cremophor vehicle (Sandimun) (5 mg/kg/sc); Group III (n = 15): animals undergoing heart transplant and administered a daily dose of pure CsA (5 mg/kg/sc). Recipient animals were sacrificed 7, 14, 21, 30 and 50 days after transplant. During the post-operative period, heart function was assessed by daily abdominal palpation. Graft specimens obtained at each follow-up period were subjected to light and transmission electron microscopy. Immunohistochemical analysis of specimens was performed using the rat macrophage-specific monoclonal antibody MCA-341. The ischaemia/reperfusion process induced considerable alteration to cardiac muscle cells of control animals. Effects, apparent after the first week of transplant, included mitochondrial swelling and loss of cristae, hypertrophy of the sarcoplasmic reticulum and structural changes to sarcomeres. Two weeks after transplant, the myocardium was infiltrated by inflammatory cells. These effects diminished 30 days post-transplant. Cardiac tissues of treated animals (groups II and III) showed similar behaviour although, in the latter group, mitochondrial damage was greater and intense myocardial fibrosis took place. Infiltration of cardiac muscle by white blood cells did not take place until 3 weeks post-implant. These results indicate: a) The ultrastructural changes detected in cardiac fibres of animals of the three study groups were attributable to the ischaemia/reperfusion process rather than to treatment with CsA; b) CsA appears to augment mitochondrial damage and myocardial fibrosis; c) the inflammatory response was delayed and reduced by the immunosupressant; and d) the cremophor administration vehicle did not seem to exert an independent toxic effect on the myocardium.     

A study of the actions of histamine on the isolated rat heart

1. The effects of histamine on cardiac force, heart rate and coronary perfusion pressure were studied in the isolated rat heart, using the Langendorff perfused heart preparation. 2. Single injections of histamine induced dose-dependent decreases in contractile amplitude, heart rate and coronary perfusion pressure. 3. Perfusions of metiamide (above 1 x 10(-4) m) had a depressant effect on contractile force and heart rate, whereas diphenhydramine (4 x 10(-6) m) reduced only the heart rate. Both agents caused a fall in coronary perfusion pressure. 4. The negative inotropic and chronotropic effects of histamine on the isolated rat heart were not significantly influenced by either metiamide of diphenhydramine, or a combination of these drugs. However, the fall in coronary perfusion pressure induced by injections of histamine was significantly antagonized by metiamide or diphenhydramine. 5. These results suggest that the effects of histamine on the isolated rat heart may not be due entirely to stimulation of H1- or H2-receptors on the cardiac muscle cells. Evidence is presented for the existence of histamine H1- and H2-receptors in the coronary vessels.     

Effects of in situ freezing and stress-shielding on the ultrastructure of rabbit patellar tendons

The effects of in situ freezing and the combination of in situ freezing and stress-shielding on the microstructure and ultrastructure of the patellar tendon were studied with use of 20 mature rabbits. The patellar tendon was frozen in situ with liquid nitrogen to kill fibroblasts and then was completely released from stress by chronically pulling a stainless-steel wire installed between the patella and the tibial tubercle. Microstructurally, the freezing treatment induced separation of collagen fiber bundles and fibroblast necrosis at 3 weeks, although the separation disappeared at 6 weeks. Ultrastructurally, small collagen fibrils with a diameter of less than 90 nm were predominant; at 6 weeks, the area occupied by collagen fibrils had decreased. In the frozen-shielded tendon, numerous large spaces were observed in the matrix at 3 weeks. This treatment increased the number of fibrils with a diameter greater than 360 nm and decreased the number of collagen fibrils per unit of area and the area occupied by collagen fibrils at 3 weeks. This study demonstrated that in situ freezing and the combination of in situ freezing and stress-shielding leads to a smaller volume of collagen fibrils per unit of cross section of the patellar tendon by mechanisms that remain to be defined.     

Cholesterol biosynthesis in stomach and intestinal tissue of rat

Biosynthesis of cholesterol and its precursors (metastenol, latosterol and 7-dehydrocholesterol) was studied in the mucous and serous membranes of small intestine, secretory and esophageal regions of the normal rat stomach. The content of these sterols was also determined. The intensity of sodium 2-14C-acetate incorporation into cholesterol and its precursors in the mucous membrane of the small intestine and stomach secretory region is considerably higher than into the same sterols of the serous membrane and esophageal region. Cholesterol synthesis is most intensive in the small intestine mucous membrane and stomach secretory region.     

Nitric oxide influences the release of histamine and glutamate in the rat hypothalamus

This study applied a social-genetic perspective to examine hypotheses concerning displays of cooperation. The sample included children from 14 monozygotic and 16 dizygotic twin pairs, organized into 30 unfamiliar partnerships. Two puzzle completion sessions were videotaped and evaluated on five dimensions of cooperation. Repeated measures of analysis of variance indicated significantly higher ratings among female than male pairs on Overall Cooperation, Mutuality of Goal and Accommodation. Contrary to expectation, social-interactional differences between unfamiliar MZ and DZ dyads were not detected. Findings are discussed with reference to new research perspectives on cooperative behavior.     

Effects of postmortem storage on the ultrastructure of the endomysium and myofibrils in normal and callipyge longissimus

These experiments were conducted to examine ultrastructural changes in longissimus from normal and callipyge lamb during 14 d of postmortem storage at 4 degrees C. Six crossbred ewe lambs (1/2 Dorset x 1/2 Romanov) were grain-fed and slaughtered at approximately 250 d of age. Leg conformation score was the basis for classifying carcasses into normal and callipyge. The normal and callipyge longissimus had mean Warner-Bratzler shear force of 2.8 (2.7, 2.4, and 3.4) and 9.0 (12.2, 6.9, and 7.9) kg, respectively, after 14 d of postmortem storage. The results of transmission electron microscopy demonstrated ultrastructural changes, including sarcolemma detachment, loss of myofibril lateral attachments, and I-band breaks in normal longissimus. Detachment of sarcolemma from myofibrils occurred in both phenotypes, but it was delayed by several days in callipyge longissimus. Thus, the sarcolemma detachment seems not to contribute significantly to postmortem tenderization. The endomysium of both phenotypes did not change with postmortem storage. In normal longissimus, the percentage of fractured I-bands increased from 0% at d 1 to 11% at d 3 (P<.05) and did not change between 3 and 14 d (15%) postmortem (P>.05). However, postmortem storage did not affect (0 to 3%) the frequency of the I-band breaks in the callipyge longissimus (P>.05). Therefore, the break in the I-band region in postmortem muscle is a change that is associated with postmortem tenderization. We conclude that the major factor responsible for the toughness of meat from callipyge longissimus is the postmortem stability of myofibrils.     

The importance of the stomach in mediating histamine-induced hypocalcemia in the rat

The effect of histamine on serum calcium homeostasis was studied in the rat. After the intravenous administration of 0.5-1.0 mg histamine base to fasted Holtzman rats weighing 80-100 g, a significant lowering of serum calcium (Ca) level occurred 30 min after injection (decrease in Ca, 1.4-1.9 mg/100 ml), but normocalcemia returned at 60 min. Repeat intravenous injections of histamine 1.0 mg resulted in repeated lowering of the serum Ca level. Hypophosphatemia did not accompany the hypocalcemia. Thyroparathyroidectomy (TPTX) did not eliminate the calcium-lowering effect of histamine in acute TPTX animals but did so in more chronic TPTX animals in which the mean serum Ca was 7.6 mg/100 ml or less. Gastrectomy, however, completely eliminated the calcium-lowering effect of histamine given in doses of up to 2 mg/rat (20 mg/kg of body weight), despite the presence of an intact thyroid gland. These studies support the role of a gastric factor and not the thyroid secretion of calcitonin in mediating this response in the rat.     

Effect of aging on gastrin receptor gene expression in rat stomach

Broiler chickens were raised in separate rooms kept at temperatures of either 27 C or 16 C from 28 through 39 days of age. At the high temperature mouth breathing was recorded, but it was absent at the lower temperature. The number of dust particles in the air was greater in the warm rooms. More than 50% of the chickens in warm rooms had microscopic lesions in the bronchi of their lungs, whereas fewer than 5% of chickens in cold rooms had such lesions. Large dust particles were visible in some of the lesions. It was postulated that the increased incidence of lung lesions in chickens from warm rooms was due to mouth breathing rather than the higher dust levels in the air of these rooms.     

Differential effects of reserpine and tetrabenazine on rat striatal synaptosomal dopamine biosynthesis and synaptosomal dopamine pools

Rat striatal dopamine (DA) levels and synaptosomal DA synthesis were determined after the administration of the catecholamine-depleting agents reserpine (RES) and tetrabenazine (TBZ). Striatal synaptosomal DA synthesis remained unchanged from control levels after Res administration over a wide range of doses (0.5-5 mg/kg) and times (up to 48 hour). In contrast, after TBZ administration, DA synthesis rapidly increased to values greater than 200% of control values, then returned to control levels. The changes in DA synthesis inversely paralleled the depletion of and recovery of striatal DA levels. The increased levels of DA synthesis did not appear to originate with alterations either in the kinetic properties of tyrosine hydroxylase or in the availability of exogenous or endogenous tyrosine. To assess the contribution of synaptosomal DA pools to the regulation of DA synthesis in tissue preparations from RES-or TBZ-pretreated animals, synaptosomal DA synthesis was assessed in the presence of DA releasing agents and compared with analogous experimental manipulations on tissue preparations from animals pretreated with alpha-methyltyrosine or the monoamine oxidase inhibitor, clorgyline. The data are consistent with a differential in vivo interaction of RES and TBZ with a nerve ending pool of DA which participates in end-product inhibition of tyrosine hydroxylase.