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Contribution of the secretory material of caecilian (amphibia: Gymnophiona) male Mullerian gland to motility of sperm: a study in Uraeotyphlus narayani.

Caecilians are a unique group of limbless burrowing amphibians with discontinuous distribution. Several caecilian species are viviparous, and all practice internal fertilization. In amniotic vertebrates the sperm undergo post-testicular physiological maturation when they are initiated into motility under the influence of an epididymal secretion. Further, during ejaculation mammalian sperm are suspended in a fluid secreted by the male accessory sex glands, viz., prostate gland and seminal vesicles. Caecilians lack comparable glands, but still practice internal fertilization. Uniquely, male caecilians retain the Mullerian ducts in the adults as a pair of functional glands. It has long been hypothesized, based on indirect evidence, that the Mullerian gland would be a male accessory sex gland, secreting a fluid in which sperm are suspended during ejaculation and which would also provide nutritional support to the ejaculated sperm. In the present study, the secretory material of the Mullerian gland of Uraeotyphlus narayani was mixed with sperm obtained from the testis, and the changes in motility were recorded. Uraeotyphlus narayani sperm possess a perforatorium of the acrosome proceeding deep into the endonuclear canal of the nucleus. The midpiece is characterized by closely applied centrioles, the anterior ends of the axoneme and axial fiber, and a mitochondrial sheath. The long tail has an undulating membrane on one side, supported by the axoneme and an axial fiber. The live sperm possess a mitochondrial vesicle, also known as the cytoplasmic droplet, anywhere along the head and the midpiece, as in anuran sperm, which is shed from sperm that have ceased motility. Uraeotyphlus narayani sperm are motile the moment they are released directly from the testis, indicating that the sperm do not require post-testicular physiological maturation. On being mixed with the secretory material of the Mullerian gland, the spermatozoa are enhanced in speed as well as duration of motility. Therefore, the caecilian male Mullerian gland is considered to be the male accessory sex gland.

Amphibians↗

Effects of a high semen-collection frequency on the quality of sperm from ejaculates and from six epididymal regions in boars.

This study examines the effect of semen-collection rhythm on the sperm maturation process in boar epididymis. Three post-pubertal boars were submitted to a high semen-collection frequency (stressed boars) during 4 days, and three males were kept as a control group (control boars). Semen samples coming from six epididymal regions and from the ejaculate of each male were evaluated for sperm concentration, sperm vitality, sperm motility and sperm morphology. In each epididymal region, either fluid resorption or fluid secretion was determined from the variation in sperm concentration. The pattern of fluid resorption-secretion along the epididymal duct differed significantly between the stressed and control boars. A high semen-collection frequency also affected the development of sperm motility and the sperm cytoplasmic droplet displacement along the epididymal duct. The incidence of some sperm abnormalities was also found to be higher in some epididymal regions and ejaculates of stressed boars. From the results of this study, it can be concluded that a high semen-collection frequency brings about an altered resorption and secretion pattern of the epididymal fluid, which results in defective sperm maturation and abnormal development of sperm motility.

Animals↗

Immunoglobulin secreting cells in normal human bronchial lavage fluids.

Immunoglobulin secreting cells were quantitated in the bronchial lavage fluids of 12 normal volunteers and compared with immunoglobulin secreting cells in peripheral blood, by a reverse hemolytic plaque assay. The mean number of cells secreting immunoglobulin (Ig)G in bronchial lavage fluids was 489 per million lymphocytes vs. a mean of 175 IgG secreting cells per million lymphocytes in peripheral blood (P < 0.02). The mean number of IgA secreting cells in bronchial lavage fluids was 633 per million lymphocytes as compared to 100 per million lymphocytes in peripheral blood (P < 0.005). Thus, compared to peripheral blood, cells from the lavage fluids were relatively enriched for both IgG and IgA secreting cells. However, IgA secreting cells were the major class of immunoglobulin secreting cells in bronchial lavage fluids, whereas IgG secreting cells predominated in peripheral blood. The prominence of IgA secreting cells in bronchial lavage fluids was further demonstrated by a mean ratio of IgA/IgG secreting cells in bronchial lavage fluids of 1.26 compared to a ratio in peripheral blood of 0.57 (P < 0.02). Cells secreting IgM were identified in only four of seven bronchial lavage fluid samples studied but in all peripheral blood samples. IgE secreting cells were not present in normal peripheral blood but could be demonstrated in 5 of 11 lavage fluid specimens. Thus, cells actively secreting immunoglobulins can be identified in the lower bronchial-alveolar tree of normal human subjects. Cells secreting IgG, IgA, or IgM may function in local lung defenses against infection; cells secreting IgE may contribute to hypersensitivity reactions in the lung.

Adult↗

Tight junctional permeability of the resting and carbachol stimulated exocrine rabbit pancreas.

The permeability of the pancreatic epithelium to horseradish peroxidase is investigated in the resting and carbachol stimulated rabbit pancreas. Horse radish peroxidase administered to the bathing medium of the isolated rabbit pancreas appears in the secreted fluid of the pancreas in a relatively low concentration. Carbachol stimulates both protein secretion and the passage of horse radish peroxidase into the secretory fluid. Histochemical assessment shows that horseradish peroxidase enters the interstitial spaces of the pancreatic tissue and is present along basal and lateral plasma membranes of acinar and ductular cells. In the absence of carbachol, horseradish peroxidase is seen more frequently in the tight junctions of ductular cells than in those of acinar cells. However, in the carbachol stimulated gland horseradish peroxidase is observed in the junctions between adjacent acinar cells more frequently than in the unstimulated gland. Freeze-fracture of acinar cells shows that the number of tight junctional strands and the tight junction depth are slightly decreased upon carbachol stimulation. The findings suggest that cholinergic stimulation of the exocrine pancreas increases the permeability of the acinar cell junctions to moderately large molecules such as horseradish peroxidase. This may result in an increase of the concentration of the molecule in the secreted fluid.

Animals↗

Role of the tryptophan residue in the interaction of pancreozymin with its receptor.

1. Analogues of the C-terminal octapeptide and tetrapeptide of pancreozymin with a modified tryptophan residue have been tested on the rat pancreas adenylate cyclase activity, on the enzyme and fluid secretion of the rat pancreas in vivo and on the amylase release from rabbit pancreatic fragments. 2. Fluorination of the tryptophan residue in position 5 or 6 does not influence the effect of the peptides on any of the measured parameters. 3. Methylation of the nitrogen atom in the indolyl ring, which eliminates hydrogen bond formation, markedly reduces the affinity of the peptides for the adenylate cyclase activity and for the amylase release in rabbit pancreatic fragments. The effects on fluid and enzyme secretion in the rat pancreas in vivo are reduced nearly as much. 4. Tetrafluorination of the tryptophan residue, which reduces its charge donor capacity, causes a still larger reduction in activity and affinity of the octapeptide. 5. The tetrafluorinated tetrapeptide stimulates the adenylate cyclase activity and the enzyme and fluid secretion in vivo more than the unmodified tetrapeptide, which may be due to its increased hydrophobicity. 6. Replacement of the nitrogen atom in the indolyl ring of tryptophan by a sulfur or an oxygen atom, which also reduces the charge donor capacity, leads again to a large reduction in the affinity and activity of both the octapeptide and the tetrapeptide. 7. These findings suggest that the charge donor capacity of the tryptophan residue is of primary importance for the biologic activity of pancreozymin, while hydrogen bond formation and hydrophobicity are of secondary importance.

Adenylyl Cyclases↗

Anti-diuresis in the blood-feeding insect Rhodnius prolixus Stål: antagonistic actions of cAMP and cGMP and the role of organic acid transport.

Secretion of primary urine by upper Malpighian tubules of the blood-sucking insect Rhodnius prolixus has recently been shown to be inhibited by cyclic GMP (cGMP). In the present work, we have demonstrated that cGMP has effects antagonistic to those of cAMP in Rhodnius tubules and have further characterized the effects of cGMP on tubular secretion. Cyclic GMP inhibited secretion at all concentrations from 5x10(-6) to 10(-3)M, though this inhibition was partially or wholly reversed by large (2mM) doses of cAMP. While sub-maximal concentrations of cGMP did not significantly alter [K(+)] and [Na(+)] of secreted fluid, high external [cGMP] reduced secretion to minimal levels and caused [K(+)] and [Na(+)] to approach pre-stimulation levels. Cyclic GMP does not appear to affect the permeability of the lower Malpighian tubule to water. Both cAMP and cGMP likely enter tubule cells by way of an organic acid transporter whose activity is induced by feeding. Sensitivity of the tubules to exogenous cGMP and cAMP, which is assumed to be a function of transport activity, reaches a peak approximately 5 days after the blood meal and declines rapidly thereafter. Transport of anions into upper tubules involves at least two different transporters: one for acylamides (e.g., p-aminohippuric acid) and another for sulphonates (e.g., amaranth, phenol red). Amaranth and phenol red blocked the actions of both cGMP and cAMP, whereas p-aminohippuric acid was without effect. This suggests that cyclic nucleotides enter by way of the sulphonate transporter.

Journal Article↗

Cytoskeletal disarrangement in rat intestinal epithelium after in vivo exposure to secretagogues.

Cholera toxin (CT) and E. coli heat-labile enterotoxin (LT) induced hypersecretion in the small intestine, as did cytochalasin B and dibutyryl-cyclic AMP (DB-cAMP). The cytoskeleton in the apical part of the intestinal epithelial cells was disorganized after challenge with either of the four secretagogues, but not cholera B-subunit toxoid, as revealed by immunofluorescence microscopy using actin and the intermediate filament keratin as markers. Electron microscopic analysis confirmed the re-engagement of the terminal web and the appearance of short microvilli lacking most of their normally observed central core of actin filaments. Pretreatment with chloroquine prevented cytoskeletal disorganization as well as hypersecretion by CT, but not by cytochalasin B. A similar effect was achieved with chloroquine on CT-induced fluid secretion, while chlorpromazine inhibited the fluid response to cytochalasin B as well as to CT. The observed cytoskeletal re-engagement might be one of the reactions behind enterotoxic diarrhoea.

Animals↗

Spatial aspects of Ca2+ signalling in pancreatic acinar cells.

Secretory cells do not only respond to an agonist with a simple rise in [Ca2+]i. It is now clear that complex patterns of [Ca2+]i elevation in terms of space and time are observed in many cell types and that these patterns may be a cellular mechanism for the regulation of different responses. Ca2+ signalling in exocrine cells of the pancreas promotes the secretion of digestive enzymes and fluid. It has been shown that at high concentrations of agonist (acetylcholine or cholecystokinin) the [Ca2+]i response is initiated in the secretory pole of the cell before spreading across the whole cell. This site of initiation of the [Ca2+]i elevation is in the region where exocytotic release of enzymes occurs and is also the site of a Ca(2+)-dependent chloride channel thought to be crucially important for fluid secretion. Lower concentrations of agonist elicit [Ca2+]i oscillations with complex repetitive patterns characteristic of each agonist. At physiological agonist concentrations, we have recently described repetitive short-lasting Ca2+ spikes that are spatially restricted to the secretory pole of the cell. In addition to these spikes, cholecystokinin also promotes slow transient Ca2+ rises that result in a global rise in Ca2+. The inositol trisphosphate (InsP3) receptor plays a crucial role in all of these various agonist responses, most of which can be reproduced by the infusion of InsP3 into the cell. The high InsP3-sensitivity of the secretory pole is postulated to be due to a localization of high-affinity InsP3 receptors. We speculate that in response to cholecystokinin the short-lasting spikes elicit exocytosis from a small 'available pool' of vesicles and that the broader oscillations induce both exocytosis and cell changes that involve movement of vesicles into this 'available pool'.

Acetylcholine↗

Variations in concentrating function of the gallbladder in the conscious monkey.

Hepatic bile is concentrated in the gallbladder by absorption of water and electrolytes. The rate of water absorption can be influenced in vitro and in vivo by gastrointestinal hormones and neurogenic transmitters. Recent studies have demonstrated that besides its absorbing activity, the gallbladder has the ability to secrete fluid into its lumen. In the present experiments, we studied the rate of net water absorption in the gallbladders of pig-tailed monkeys sitting in restraining chairs. Bile from the common bile duct and the gallbladder was led out through cannulas to a stream splitter, samples were obtained, and bile was returned to the duodenum. By measuring outflow from the gallbladder and the concentration of bile acids in hepatic bile and bile that had passed through the gallbladder, net water absorption from the gallbladder bile could be calculated. The results demonstrate that during daytime fasting there was a net absorption corresponding to 30% of the fasting gallbladder volume per hour, and after feeding there was a net secretion of fluid into the gallbladder lumen. Compared with the awake fasting state, net water absorption from the gallbladder decreased at night while the animal was fasting and asleep. Physiologically, secretion of fluid after a meal could help to empty the gallbladder, and changes in net water absorption by the gallbladder could influence the kinetics of the enterohepatic circulation of bile acids.

Absorption↗

Secretagogue-induced 86Rb+ efflux from bovine parotid is HCO3- dependent.

Muscarinic agonist (carbachol)-induced K+ loss from a bovine parotid mince was studied using 86Rb+ as a K+ marker. In contrast to our previous studies with the rat parotid [Am. J. Physiol. 261 (Gastrointest. Liver Physiol. 24): G111-G118, 1991] in which both Cl(-)-dependent and HCO3(-)-dependent components of carbachol-induced 86Rb+ efflux were observed, no significant evidence for Cl(-)-dependent 86Rb+ loss was detected in the bovine parotid. HCO3(-)-dependent agonist-induced 86Rb+ loss was blunted by K+ and Cl- channel blockers and by removal of extracellular Ca2+, consistent with the hypothesis that this 86Rb+ loss occurs via a Ca(2+)-activated K+ channel and that this cation loss serves to electrically balance the concomitant loss of HCO3- via an electrically conductive pathway, presumably an apical anion channel. Acetate, formate, and propionate could substitute for HCO3-. Interpreted in terms of current models of salivary fluid secretion, which hypothesize that the production of fluid is secondary to anion secretion accompanied by an electrically coupled K+ loss, these results indicate that salivary production in the bovine parotid is driven almost exclusively by acinar HCO3- secretion.

Animals↗

The physiological uterine secretion of rats and its activity in dispersing ovum cumulus cells in vitro.

The quantity of physiological uterine fluid secreted by rats exhibiting a regular four-day sexual cycle was measured at every stage and the freshly ovulated rat ova, surrounded by their cumulus cells, were incubated at 37 degrees C in this secretion sample. The results showed that the fluid began to be secreted on the morning of vaginal pro-oestrus and increased steadily for about 24 h. Two declines in quantity are observed, a slight one at the end of pro-oestrus and a marked one about 4 hours after the start of vaginal oestrus which coincided with ovulation. No secretion is obtained either at metaoestrus or at dioestrus. Only the secretion at the oestrus stages caused total dispersion of the corona cells in vitro. This property is retained after freezing, heating to 60 degrees C and lyophilization. A correlation with plasma sexual hormone measurement and some fertility factor contained in uterine secretion was discussed in relation to this dispersing activity.

Animals↗

The area postrema lesions alter the inhibitory effects of peripherally infused pancreatic polypeptide on pancreatic secretion.

Circulating PP binds to specific receptors in the DVC through the AP, but the mechanism through which these brain receptors affect pancreatic secretion is not clear. We hypothesize that the removal of the AP (APX) will alter the effects of PP on pancreatic secretion. APX or sham procedures were performed in anesthetized male Wistar rats. After a 1-month recovery, one group of rats were infused with either PP (30 or 100 pmol/kg per h) or vehicle under basal or 2-DG-stimulated (75 mg/kg, i.v. bolus) conditions for studying pancreatic exocrine secretion. A second parallel group was sacrificed for examination of PP receptor binding in the brain stem. A third group received an intraperitoneal injection of PP at the dose of 4.15x10(4) pmol/kg (200 microg/kg) and c-fos expression in the brain stem was examined. APX eliminated PP binding sites in the DVC as assessed by autoradiography. PP infusion caused a dose-dependent decrease in basal protein secretion. APX partially reversed PP inhibition of basal protein secretion when infused at 30 pmol/kg per h, and at 100 pmol/kg per h stimulated pancreatic fluid secretion and reversed the inhibition of protein secretion. During 2-DG stimulation the effects of PP and 2-DG on pancreatic fluid and protein secretion were parallel. PP dose-dependently inhibited 2-DG-stimulated secretion in sham rats. APX reduced the pancreatic fluid (54%) and protein (46%) secretory response to 2-DG. However, PP at 30 pmol/kg per h remained a potent inhibitor of 2-DG-stimulated pancreatic secretion in APX rats. This effect was blunted with PP at 100 pmol/kg per h in APX rats, possibly related to the stimulatory effect of high-dose PP in APX rats without 2-DG. Furthermore, i.p. PP induced significantly greater c-fos activation of NTS neurons in APX rats than sham rats, despite the apparent absence of PP binding sites in the DVC. We conclude that in awake rats, PP inhibits basal secretion, in part, through the AP. Furthermore, and unlike PYY, PP inhibits 2-DG-stimulated pancreatic secretion, and it does so through an AP-independent mechanism. The possibility that the mechanism may involve the DVC cannot be excluded since i.p. injection of PP activates c-fos expression in DVC neurons. Thus, PP and PYY may regulate different components of the pancreatic secretory control system through unique pathways.

Animals↗

Lung fluid restriction affects growth but not airway branching of embryonic rat lung.

During the later stages of fetal life lung growth and development is dependent upon a variety of factors, including a normal amount of liquid within the lung's lumen. To investigate whether embryonic lung epithelium secretes fluid and whether lung liquid is essential for proper embryonic airway lung growth and branching, we incubated 12-day rat lung primordia (term=22 days) in submersion culture in serum-free medium for 48 h in room air (21% O2/5% CO2). Under these conditions, lung growth and branching proceeded but at a slower rate when compared to growth and branching in vivo. Neither addition of serum nor incubation in a fetal O2 concentration (=3% O2) changed the growth rate or the degree of branching in vitro. The luminal area of the explant increased progressively with time in culture. Inhibitors of active Cl- secretion (200 microM bumetanide and 1 mM furosemide) significantly reduced the lumen size compared with control. A similar effect was noted with lung explants of 13-15 days of gestation. Branching morphogenesis was not impaired by lung fluid reduction. Reduction of luminal liquid significantly increased DNA synthesis of 12-day embryonic lung explants, but this effect of bumetanide and furosemide on DNA synthesis was reversed when 13-15 day lung explants were used. These data suggest that embryonic lung epithelium secretes fluid and that the secretion is chloride dependent. Lung fluid is involved in controlling lung growth but not branching of the embryonic rat lung.

Aerobiosis↗

Secretory immunoglobulin A response to Shiga toxin in rabbits: kinetics of the initial mucosal immune response and inhibition of toxicity in vitro and in vivo.

Although the role of Shiga toxin in dysentery is unknown, the toxin is cytotoxic to HeLa cells, causes fluid secretion in rabbit intestine, and is lethal to rabbits and mice when injected parenterally. In the present study, rabbits received three weekly doses of Shiga toxin directly into chronically isolated ileal loops. Within a week, secretions from these loops contained immunoglobulin A (IgA) anti-Shiga toxin. The titer of IgA anti-Shiga toxin increased after weekly doses 2 and 3. Little IgG anti-Shiga toxin was present in loop secretions, although high titers of IgG anti-Shiga toxin were found in the sera. These loop secretions were able to neutralize the cytotoxic effects of Shiga toxin in the HeLa cell assay. The capacity to neutralize the cytotoxicity of the toxin correlated strongly with the IgA anti-Shiga toxin titer in these same secretions. Pooled immune loop secretions were also able to significantly reduce fluid accumulation in acutely ligated loops in rabbits, while loop secretions from control rabbits could not. Shiga toxin elicited a strong secretory IgA response upon application to the intestine. Further, the mucosal antibodies produced functioned to prevent the toxic effects of Shiga toxin both in vitro and in vivo.

Animals↗

Characterization of the opiate receptor population mediating inhibition of VIP-induced secretion from the small intestine of the rat.

Net water transport was measured from the jejunum of anaesthetized rats by a re-circulation technique. Several narcotic analgesics were administered intravenously and assessed for activity in reversing net fluid secretion induced by intra-arterial infusion of vasoactive intestinal peptide (VIP). The mu-opiate agonists, morphine, RX 783006 and FK 33-824 produced full reversal of the secretory phase of the VIP response, but failed to restore totally fluid transport to the control level of net absorption. The kappa-agonist, ethylketocyclazocine, caused only partial reversal of VIP-induced secretion while the more selective kappa-agonist, MR 2034, produced a small though non-significant antisecretory effect at high doses. The delta-agonist, D-Ala2-D-Leu5-enkephalin also had negligible antisecretory activity. Naloxone caused a parallel displacement to the right of the antisecretory dose-response line to morphine. The 'in vivo pA2' value of naloxone was 7.14. The results are compared with previously published antinociceptive activities of the opiate agonists and in vivo pA2 values of naloxone. It is concluded that stimulation of mu-opiate receptors mediates inhibition of VIP-induced fluid secretion from the rat jejunal mucosa.

Analgesics, Opioid↗

The restricted penetration of iodinated rat FSH and LH into the seminiferous tubules of the rat testis.

The penetration of 125I-iodinated rat follicle-stimulating hormone (FSH; labelled by three different techniques) and luteinizing hormone (LH) through the walls of the seminiferous tubules of the rat testis has been studied by injecting the labelled hormone into rats with the efferent ducts of one testis ligated 16 h before the collection of samples of blood and tissues. The concentration of trichloracetic acid-precipitable and immunoprecipitable radioactivity was measured in blood plasma and rete testis fluid and calculated for the total secreted fluid retained in the testis by the ligature, and for the additional tubular fluid from the ligated testis, separated by centrifugation after decapsulating the testis and dispersing the cells. Very little intact hormone penetrated into the testicular fluids, even 16 h after injection of the labelled hormone, and the volume of distribution in the unligated testis of the trichloracetic acid-precipitable radioactivity was only slightly greater than that for markers known to be confined to the extracellular interstitial fluid. This suggests that the labelled hormones do not penetrate readily through the walls of the semiferous tubules into their lumina. Injected inorganic iodiide and trichloracetic acid-soluble 125I-circulating after the injection of iodinated hormones penetrated more rapidly into the tubules, but had not reached equilibrium between the testicular fluids and blood plasma 16 h after injection. Labelled FSH was reasonably stable in the circulation after injection, but 80% of the 125I was not protein-bound 16 h after injection of labelled LH.

Animals↗

Growth hormone reduces chloride secretion in human colonic epithelial cells via EGF receptor and extracellular regulated kinase.

BACKGROUND AND AIMS: Growth hormone (GH) has been shown to alleviate symptoms in patients with Crohn's disease. Chloride secretion is important in driving intestinal fluid secretion. We examined whether GH inhibits chloride secretion induced by carbachol (CCh, a calcium-dependent pathway), and the downstream effectors responsible. METHODS: T(84) cells were pretreated with GH at various concentrations followed by CCh (100 micromol/L). Chloride secretion was assessed as changes in short circuit current ( triangle up I(sc)) in Ussing chambers. Tyrphostins AG1478 (an epidermal growth factor receptor [EGFr] inhibitor) and AG490 (a Janus kinase 2 [JAK2] inhibitor), SB203580 (a p38 inhibitor), and PD98059 (a MEK1 inhibitor) were used. RESULTS: GH inhibited CCh-induced chloride secretion at up to 10 nmol/L, but higher concentrations were less effective. GH caused tyrosine phosphorylation of JAK2 and EGFr. AG490 suppressed activation of JAK2 and EGFr in response to GH. AG1478 prevented GH activation of EGFr and reversed its inhibitory effect on chloride secretion. GH also induced activation of both p38 and ERK1/2. AG490 reversed GH-induced tyrosine phosphorylation of both ERK1/2 and p38, but AG1478 reversed that of ERK1/2 only. PD98059, but not SB203580, reversed the inhibitory effect of GH on chloride secretion. CONCLUSIONS: GH inhibits CCh-induced chloride secretion via a JAK2-dependent mechanism involving transactivation of EGFr and consequent recruitment of ERK1/2. Although activated, p38 does not contribute to the inhibitory effect of GH on secretion. These data elucidate mechanisms of GH inhibition of chloride secretion in intestinal epithelia, which may be relevant to therapeutic benefits of GH in Crohn's disease or other diarrheal diseases.

Biological Transport↗

Adrenergic mediation of the intestinal antisecretory action of opiates administered into the central nervous system.

The antisecretory effects of the stable enkephalin analogs, [D-Ala2-Met5] enkephalinamide (DAMA) and [D-Ala2-D-Leu5] enkephalin, and the opiate drug morphine were evaluated on fluid secretion induced by cholera toxin in isolated loops of the jejunum and proximal and distal ileum in anesthetized rats. Intracerebroventricular administration of DAMA (0.03-3 micrograms) or [D-Ala2-D-Leu5] enkephalin (1.0-10 micrograms) dose-dependently reduced secretion in the jejunum without affecting fluid movement in the other small intestinal segments. Morphine in doses up to 30 micrograms i.c.v. had no significant antisecretory effects. Intravenous administration of DAMA, at doses up to 3000 micrograms/kg, had little effect on intestinal fluid accumulation. The antisecretory action of DAMA (3 micrograms i.c.v.) was completely blocked by pretreatment with the alpha adrenergic antagonist phentolamine and after peripheral sympathectomy induced by guanethidine. In contrast, DAMA activity was preserved in adrenal demedullated rats. DAMA had no significant effects upon mean arterial blood pressure or on blood acid-base balance. These results suggest that the antisecretory effects of opiates are, at least partly, mediated at sites within the central nervous system. These actions are probably a consequence of increased activity in sympathetic nerve fibers innervating the upper small intestine.

Animals↗