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PubMed1984

A lower esophageal sphincter reflex involving substance P.

The purpose of this study was to determine the mechanism by which distal esophageal acidification increases lower esophageal sphincter (LES) pressure in the anesthetized cat. Intraluminal pressures and myoelectric activity were recorded using fixed, localized manometric catheters and serosal bipolar silver-silver chloride electrodes. The increase in LES pressure (27.1 +/- 4.9 mmHg) and spike activity (133.8 +/- 22.6 spikes/min) following distal esophageal acidification were greater than after saline (P less than 0.001). These responses were abolished by either tetrodotoxin (intravenously) or intraluminal ethyl aminobenzoate. The responses were not antagonized by bilateral cervical vagotomy or by atropine, hexamethonium, phentolamine, propranolol, diphenhydramine, cimetidine, cinanserin, naloxone, haloperidol, or proglumide. Tachyphylaxis to substance P abolished the LES pressure and spike responses to exogenous substance P and to distal esophageal acidification but had no effect on the LES responses to phenylephrine (25.0 micrograms/kg iv) or pentagastrin (0.5 microgram/kg iv). The putative substance P antagonist [D-Pro2,D-Trp7,9]substance P was a partial antagonist and a weak agonist on the LES. Large doses of [D-Pro2,D-TRP7,9]substance P (200.0 micrograms/kg iv) gave a 61.3 +/- 19.3% inhibition of the LES pressure response to acid (P less than 0.05). Intravenous tetrodotoxin partially antagonized the LES response to substance P (10.0 micrograms/kg iv). These studies suggest that the increases in LES pressure and spike activity following distal esophageal acidification occur through a spike-associated enteric neural reflex that involves substance P as a neurotransmitter.

Action Potentials↗
PubMed1984

Discovery of a cholecystokinin analogue with partial agonist activity.

In dispersed acini from guinea pig pancreas, cholecystokinin-(27-32)-amide [CCK-(27-32)-NH2] did not stimulate amylase secretion and inhibited the stimulation caused by CCK-(26-33). In dispersed acini from mouse or rat pancreas, CCK-(27-32)-NH2 stimulated amylase secretion. The stimulation of amylase secretion caused by a maximally effective concentration of CCK-(27-32)-NH2 was less than that caused by a maximally effective concentration of cholecystokinin-(26-33), and in contrast to the action of cholecystokinin-(26-33) supramaximal concentrations of CCK-(27-32)-NH2 did not cause submaximal stimulation of amylase secretion. Dibutyryl cGMP and proglumide each inhibited the stimulation of amylase secretion caused by CCK-(27-32)-NH2. CCK-(27-32)-NH2 inhibited binding of 125I-labeled CCK to mouse and rat pancreatic acini. These results indicate that, in mouse and rat pancreatic acini, CCK-(27-32)-NH2 is a partial agonist and that this partial agonist activity is produced by occupation of the CCK receptor by CCK-(27-32)-NH2.

Amylases↗
PubMed1984

Characterization of cholecystokinin receptors on bovine gallbladder membranes.

Cholecystokinin (CCK) binding to its receptors on a muscularis membrane fraction of bovine gallbladder was characterized using a biologically active CCK-33-[125I]Bolton-Hunter conjugate. Receptor binding was localized to the muscularis layer of the gallbladder; no binding was seen on either mucosal or serosal membranes. At 24 degrees C and pH 6.5, binding was maximal after 60-90 min of incubation, remained at a plateau for at least 240 min, and was reversed by the addition of unlabeled CCK-8. Optimal binding was seen at pH of 5.5 and required the presence of magnesium. Gallbladder binding data, best fit by a two-parameter model using a nonlinear least-squares computer program, was consistent with a single order of binding sites with a Kd of 618 +/- 168 pM and a binding capacity of 100.5 +/- 15.7 fmol/mg prot (mean +/- SE, n = 5). CCK-8 and CCK-33 inhibited 125I-CCK binding to gallbladder membranes with similar potencies, whereas desulfated CCK-8, gastrin I and II, and CCK-4 were at least 500 times less potent than CCK-33. The CCK antagonists dibutyryl cGMP and proglumide inhibited 125I-CCK binding with an IC50 of 31 and 600 microM, respectively. The present studies therefore demonstrate the existence of a specific CCK receptor on bovine gallbladder muscularis membranes with a high degree of selectivity for CCK analogues.

Animals↗
PubMed1984

Gastrin receptors on nonparietal cells isolated from canine fundic mucosa.

The cellular localization of gastrin receptors was studied using dispersed canine fundic mucosal cells. In previous studies 125I-[Leu15]gastrin-17 (125I-[Leu15]G-17) binding was found to parietal cells, but gastrin binding was also found in the small-cell elutriator fractions (SCEF). In the present study a density gradient was used to further separate the SCEF and the distribution of 125I-[Leu15]G-17 binding correlated with cellular content of somatostatinlike immunoreactivity (SLI). In contrast, 125I-[Leu15]G-17 binding was inversely correlated with the histamine content of the fractions. 125I-[Leu15]G-17 binding to the SCEF was rapid and reversible. Total binding was 0.29 +/- 0.02 fmol/10(6) cells (mean +/- SE, n = 15); excess unlabeled G-17 inhibited 85% of this binding. G-17, [Leu15]G-17, and 127I-[Leu15]G-17 were equipotent in inhibiting 125I-[Leu15]G-17 binding and stimulating SLI secretion from the SCEF placed in short-term culture, whereas 127I-G-17 had a low potency for both effects. Proglumide, known to inhibit cholecystokinin binding to pancreatic acinar cell receptors, also inhibited 125I-[Leu15]G-17 binding to the SCEF and inhibited G-17 stimulated SLI release. We conclude that in the canine fundic mucosa gastrin interacts with receptor sites on parietal cells and somatostatin cells but probably not on fundic mucosal histamine-containing cells. These receptor sites for gastrin may activate counterbalancing mechanisms regulating the secretion of acid.

Animals↗
PubMed1985

Receptors for mammalian tachykinins on isolated intestinal smooth muscle cells.

The existence of receptors for three mammalian tachykinins, substance P (SP), substance K (SK), and neuromedin K (NK), was examined in smooth muscle cells, isolated separately from the longitudinal and circular muscle layers of guinea pig ileum. Tachykinin receptors capable of mediating contraction were present in muscle cells from both layers. The receptors were selectively blocked by the tachykinin antagonist [D-Pro2, D-Trp7,9]substance P but not by muscarinic, gastrin/cholecystokinin, or opiate antagonists (0.3 nM atropine, 1 mM proglumide, and 0.3 nM naloxone, respectively). The rank order of potency of tachykinins in causing contraction, NK greater than SP greater than SK, was similar in both muscle cell types. The results obtained in isolated muscle cells were closely paralleled by results obtained in intact muscle strips; the main difference was the greater sensitivity of isolated cells to tachykinin agonists (250-fold) and antagonist (210-fold). The inhibitory dissociation constant (Ki) of [D-Pro2, D-Trp7,9]substance P estimated from the displacement of dose-response curves (muscle cells) or from Schild plots (muscle strips) differed minimally or not at all, when either SP or SK was used as agonist, consistent with interaction of the two peptides with the same receptor subtype. The notion of a single receptor subtype in ileal muscle cells of the guinea pig was further supported by the occurrence of complete cross-desensitization between SP and SK in muscle strips.

Animals↗
PubMed1986

Cholecystokinin mediates feedback regulation of pancreatic enzyme secretion in rats.

Previous studies have shown that trypsin and chymotrypsin in the duodenum exert a negative-feedback regulation on pancreatic enzyme secretion in the rat. The mechanism responsible for this physiological phenomenon is unknown. By use of a specific and sensitive bioassay based on amylase release from isolated pancreatic acini, the role of cholecystokinin in the negative-feedback regulation of exocrine pancreatic secretion was examined. Rats were prepared with duodenal cannulas and pancreaticobiliary cannulas. Diversion of pancreaticobiliary juice resulted in a threefold increase in pancreatic protein output and an increase of plasma cholecystokinin from a basal level of 0.5 +/- 0.08 pM cholecystokinin octapeptide (CCK-8) to 16 +/- 4 pM CCK-8. Perfusion of trypsin (2 mg/h) or pancreaticobiliary juice returned pancreatic protein output to basal levels and plasma cholecystokinin to 2.1 +/- 1.2 and 0.33 +/- 0.1 pM, respectively. The inhibitory effect of trypsin on cholecystokinin release was enzyme and site specific, since inhibition of cholecystokinin release was not observed with perfusion of amylase into the duodenum or with trypsin into the ileum. Intravenous infusion of proglumide abolished the increase in pancreatic secretion following diversion of pancreaticobiliary juice. Intraduodenal perfusion of lidocaine, infusion of tetrodotoxin into the superior mesenteric artery, or intravenous infusion of atropine inhibited the rise in plasma cholecystokinin seen with diversion of pancreaticobiliary juice. These studies suggest that feedback regulation of pancreatic enzyme secretion in the rat is mediated by release of cholecystokinin. Furthermore, the feedback mechanism is neurally mediated, involving a cholinergic pathway.

Animals↗
PubMed1987

Characterization of gastrin receptors on guinea pig pancreatic acini.

Recent studies have demonstrated gastrin receptors in some pancreatic tumors and that gastrin is a potent stimulant of pancreatic Na+-H+ exchange. In the present study we used 125I-labeled gastrin (125I-gastrin) to characterize gastrin receptors on guinea pig pancreatic acini. Binding of 125I-gastrin was temperature dependent, saturable, and specific for gastrin-related peptides. Analysis demonstrated a single class of receptors with high affinity for gastrin (Kd = 1.5 nM) and a binding capacity of 1 fmol/mg protein. Binding of 125I-gastrin was inhibited with the following relative potencies (Kd): cholecystokinin octapeptide (CCK-8) (0.35 nM) greater than gastrin-17-I = gastrin-34-I (1.5 nM) greater than pentagastrin (7 nM) greater than desulfated [des(SO3)]CCK-8 (28 nM) greater than CCK-4 (508 nM) and by the receptor antagonists CBZ-CCK-27-32-NH2 (3.5 microM) greater than proglumide analogue 10 (30 microM) greater than asperlicin (265 microM) greater than Bt2-guanosine 3',5'-cyclic monophosphate (828 micron). In contrast, for both stimulation of enzyme secretion and inhibition of binding of 125I-CCK-8 the relative potencies were CCK-8 much greater than des(SO3)CCK-8 greater than gastrin-17-I = gastrin-34-I greater than pentagastrin greater than CCK-4. For each receptor antagonist the dose-inhibition curve for gastrin-stimulated amylase release was superimpossible with that for CCK-8-stimulated amylase release. Gastrin-17-I at concentrations less than 0.1 microM did not potentiate carbachol or vasoactive intestinal peptide-stimulated amylase secretion and did not affect basal or stimulated adenosine 3',5'-cyclic monophosphate or 45Ca outflux.(ABSTRACT TRUNCATED AT 250 WORDS)

Amylases↗
PubMed1988

Comparison of gastrointestinal responses to CCK-8 and associated with vomiting.

The gastrointestinal motor and myoelectric responses associated with vomiting induced by apomorphine (APO) and activated by cholecystokinin octapeptide (CCK-8) were compared as well as the mechanisms of initiation of these responses. Twelve dogs were surgically implanted with strain-gauge force transducers or bipolar electrodes for chronic recording of contractile or electrical activity. The responses to CCK-8 were determined in the fasted state and compared with the gastrointestinal motor and myoelectric correlates of vomiting activated by APO. After recording control responses, the effects of the following agents on these responses were determined: atropine, domperidone, and proglumide. In addition, the effects of supradiaphragmatic vagotomy or splanchnicectomy were determined. We found that CCK-8 activated contractile and myoelectric responses in the absence of vomiting, which were similar in most respects to those found in association with vomiting. These responses included 1) the retrograde giant contraction (RGC) and 2) the post-RGC phasic contractions. These RGCs were similar with respect to their activation in an all-or-none fashion, magnitude, duration, and position in the small intestine. The myoelectric correlates of these motor responses were similar qualitatively and quantitatively. The responses activated by APO and CCK-8 differed with respect to their coordination at different levels of the gastrointestinal tract. Whether activated by CCK-8 or APO, atropine blocked the RGC but not the post-RGC contractions. Domperidone blocked all responses to APO but not to CCK-8, and splanchnicectomy did not affect responses to either agent. Vagotomy blocked all gastrointestinal responses to APO but not to CCK-8. These results indicated that CCK-8 activates the gastrointestinal motor and myoelectric correlates of vomiting by a peripheral mechanism that does not include dopamine receptors.

Animals↗
PubMed1990

Characterization of cholecystokinin receptors on the sphincter of Oddi.

To characterize directly the ability of cholecystokinin (CCK) to interact with receptors on the sphincter of Oddi (SO), we measured binding of 125I-labeled Bolton-Hunter-labeled COOH-terminal octapeptide of cholecystokinin (125I-BH-CCK-8) to tissue sections from the guinea pig SO. Autoradiography localized binding of 125I-BH-CCK-8 over the SO smooth muscle layer. Binding was saturable, specific, dependent on time, pH, and temperature, and was reversible. Binding of 125I-BH-CCK-8 was inhibited by various CCK receptor agonists with the following potencies: CCK-8 much greater than des(SO3)CCK-8 much greater than gastrin-17-I and by various CCK receptor antagonists with the following potencies: L-364,718 greater than proglumide analogue 10 much greater than carbobenzoxy-Tyr(SO3H)-Met-Gly-Trp-Met-Asp-NH2 greater than N2,O2' dibutyryl guanosine 3',5'-cyclic monophosphate. The potencies of agonists in stimulating and of antagonists in inhibiting CCK-8-stimulated SO contractions correlated closely with their abilities to inhibit binding of 125I-BH-CCK-8. Analysis of binding of 125I-BH-CCK-8 to SO tissue sections revealed two classes of CCK binding sites: a high-affinity site [dissociation constant (Kd) 0.2 nM] and a low-affinity site (Kd 70 nM). Atropine or tetrodotoxin (TTX) caused a similar rightward shift of the CCK-8 dose-response curve for stimulation of SO contraction. Comparison of receptor occupation to CCK-8-induced contraction suggested that CCK-8 occupation of the high-affinity binding site correlated with contraction in the absence of atropine and the low-affinity CCK binding with contraction in the presence of atropine or TTX.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Mechanism of action of the anti-shock effect of CCK-8: influence of CCK antagonists and of sympatholytic drugs.

In an experimental model of haemorrhagic shock that causes 100% mortality in rats within 30 min, the intravenous bolus injection (20 micrograms/kg) of sulfated cholecystokinin octapeptide (CCK-8) induces a prompt and sustained rise in blood pressure and pulse amplitude, all treated animals still surviving at the end of the experiment (2 h). This effect of CCK-8 is completely blocked by reserpine (5 mg/kg i.p.), significantly antagonized by prazosin (0.1 mg/kg i.v.) and yohimbine (1 mg/kg i.v.), and unaffected by practolol (15 mg/kg i.v.) and proglumide (0.2 mg/kg i.v.); it is completely antagonized by the intravenous (0.01-0.05 mg/kg), but not by the intracerebroventricular (0.002 mg/kg) injection of the 'peripheral' CCK antagonist, L-364,718. The present data indicate that the cardiovascular effects of CCK-8 in haemorrhagic shock involve peripheral CCK receptors, and require the functional integrity of the sympathetic nervous system.

Animals↗
PubMed1986

Evidence that cholecystokinin octapeptide (CCK-8) acts as a potent, full agonist on gastrin receptors for acid secretion in the isolated mouse stomach: lack of antagonism by the specific CCK antagonist asperlicin.

Cholecystokinin octapeptide (CCK-8) (EC50 = 5 nM) was considerably more potent than pentagastrin (EC50 = 161 nM) in stimulating acid secretion in the isolated perfused mouse stomach suspended in a medium containing a phosphodiesterase inhibitor. The maximum acid response to CCK-8 was not significantly different from that produced by pentagastrin. The nonselective CCK/gastrin antagonist, proglumide, but not the selective CCK antagonist, asperlicin, antagonized the acid response to both pentagastrin and CCK-8. The data suggest that CCK-8 acts as a potent, full agonist on gastrin receptors for acid secretion in the isolated mouse stomach.

Animals↗
PubMed1984

Gastrin receptors on isolated canine parietal cells.

The receptors in the fundic mucosa that mediate gastrin stimulation of acid secretion have been studied. Synthetic human gastrin-17-I (G17) with a leucine substitution in the 15th position ( [Leu15]-G17) was iodinated by chloramine T; high saturable binding was found to enzyme-dispersed canine fundic mucosal cells. 127I-[Leu15]-G17, but not 127I-G17, retained binding potency and biological activity comparable with uniodinated G17. Fundic mucosal cells were separated by size by using an elutriator rotor, and specific 125I-[Leu-15]-G17 binding in the larger cell fractions was highly correlated with the distribution of parietal cells. There was, however, specific gastrin binding in the small cell fractions, not accounted for by parietal cells. Using sequential elutriation and stepwise density gradients, highly enriched parietal and chief cell fractions were prepared; 125I-[Leu15]-G17 binding correlated positively with the parietal cell (r = 0.98) and negatively with chief cell content (r = -0.96). In fractions enriched to 45-65% parietal cells, specific 125I-[Leu15]-G17 binding was rapid, reaching a steady state at 37 degrees C within 30 min. Dissociation was also rapid, with the rate similar after 100-fold dilution or dilution plus excess pentagastrin. At a tracer concentration from 10 to 30 pM, saturable binding was 7.8 +/- 0.8% per 10(6) cells (mean +/- SE) and binding in the presence of excess pentagastrin accounted for 11% of total binding. G17 and carboxyl terminal octapeptide of cholecystokinin (26-33) were equipotent in displacing tracer binding and in stimulating parietal cell function ( [14C]aminopyrine accumulation), whereas the tetrapeptide of gastrin (14-17) had a much lower potency. Proglumide inhibited gastrin binding and selectively inhibited gastrin stimulation of parietal cell function. Canine parietal cells have specific receptors for gastrin that mediate stimulation of parietal cell function. Gastrin receptors were undetectable on chief cells, and yet present on another smaller mucosal cell(s).

Aminopyrine↗
PubMed1993

The effect of cholecystokinin on intracellular Ca2+, membrane-associated protein kinase-C activity, and progesterone production in chicken granulosa cells.

Nerve fibers immunoreactive for cholecystokinin (CCK) have been observed in the rat ovary, but the function of this gut peptide in the ovary is not known. These studies were designed to investigate the effects of the CCK C-terminal octapeptide (CCK-8) on the intracellular calcium ion concentration ([Ca2+]i), protein kinase-C (PKC) activity, and progesterone secretion in granulosa cells obtained from the two largest preovulatory follicles (F1 and F2) of hens. [Ca2+]i was measured in cells loaded with the Ca(2+)-responsive fluorescent dye fura-2. The resting [Ca2+]i in these cells was 96 +/- 5 nM. There was a rapid (i.e. within 5-10 sec) 2- to 4-fold increase in [Ca2+]i in 70% of the cells examined after the addition of 10(-7) M CCK-8. The CCK-8-triggered [Ca2+]i transient was not affected by incubating the cells in Ca(2+)-free medium containing 2 mM EGTA or by pretreating the cells with a Ca2+ channel blocker, such as La3+ (1 mM) or D600 (100 microM). The CCK-8-triggered [Ca2+]i surge was abolished by pretreating the cells with the inhibitor of inositol phospholipid hydrolysis, neomycin (1.5 mM), the CCK antagonists proglumide (1 mM) and benzotript (1 mM), or pertussis toxin (50 ng/ml for 12 h). Incubating granulosa cells with CCK-8 (2 x 10(-7) M) for 10 min stimulated a 1.60 +/- 0.04-fold increase in membrane-associated PKC activity over control levels. In 3-h incubations, CCK-8 (10(-6)-10(-8) M) did not affect basal or LH (20 or 100 ng/ml-stimulated progesterone production. These studies demonstrate that CCK-8 causes a transient increase in chicken granulosa cell [Ca2+]i through the release of Ca2+ from intracellular stores and activates membrane-associated PKC activity, but does not affect progesterone production. These results suggest the presence of G-protein-coupled phospholipase-C-activating CCK receptors on the surface of these cells.

Animals↗
PubMed1991

[Effects of gabexate mesilate (FOY) on the gallbladder, sphincter of Oddi and duodenum of the normal and gastrectomized dogs].

FOY induced a dose-dependent inhibitory response on the gallbladder, sphincter of Oddi and duodenum of normal and gastrectomized dogs, although it induced an excitatory response in some dogs. The inhibitory response was not reduced or terminated by pretreatment with atropine, guanethidine, hexamethonium or/and proglumide. The FOY-induced inhibitory response reversed to the excitatory response in the sphincter of Oddi and duodenum by pretreatment with tetrodotoxin, but not in the gallbladder. These results suggested that the FOY-induced inhibitory response of the sphincter of Oddi and duodenum was caused by stimulation of nonadrenergic noncholinergic inhibitory neurons, not by FOY-induced cholecystokinin secretion. The excitatory response was induced by direct stimulation of their smooth muscles. The inhibitory response of the gallbladder to FOY was induced by direct stimulation of the smooth muscles.

Animals↗
PubMed1986

[Receptive relaxation of the canine stomach].

Receptive relaxation of the stomach by feeding was studied in 5 conscious dogs by means of chronically implanted force transducers on the gastric body and antrum. It was found that only the gastric body but not antrum relaxed by feeding, and magnitude of the relaxation of the gastric body was linearly related to the volume (5, 10 and 20 g/kg) of test meals, given once or in multiple times. Secondly, in the study of pharmacological blockers, it was found that atropine, hexamethonium and phentolamine significantly inhibited relaxation, while naloxone and proglumide significantly suppressed relaxation in 3 dogs. Propranolol and domperidone did not influence on receptive relaxation. It is concluded that receptive relaxation of the stomach is mainly mediated through a cholinergic reflex, however, involvement of neurotransmitters other than acetlycholine is suggested in the regulation of receptive relaxation.

Afferent Pathways↗
PubMed2006

Activation of neural cholecystokinin-1 receptors induces relaxation of the isolated rat duodenum which is reduced by nitric oxide synthase inhibitors.

Cholecystokinin (CCK) influences gastrointestinal motility, by acting on central and peripheral receptors. The aim of the present study was to determine whether CCK has any effect on isolated duodenum longitudinal muscle activity and to characterize the mechanisms involved. Isolated segments of the rat proximal duodenum were mounted for the recording of isometric contractions of longitudinal muscle in the presence of atropine and guanethidine. CCK-8S (EC50: 39; 95% CI: 4.1-152 nM) and cerulein (EC50: 58; 95% CI: 18-281 nM) induced a concentration-dependent and tetrodotoxin-sensitive relaxation. Nomeganitro-L-arginine (L-NOARG) reduced CCK-8S- and cerulein-induced relaxation (IC50: 5.2; 95% CI: 2.5-18 microM) in a concentration-dependent manner. The magnitude of 300 nM CCK-8S-induced relaxation was reduced by 100 microM L-NOARG from 73 +/- 5.1 to 19 +/- 3.5% in an L-arginine but not D-arginine preventable manner. The CCK-1 receptor antagonists proglumide, lorglumide and devazepide, but not the CCK-2 receptor antagonist L-365,260, antagonized CCK-8S-induced relaxation in a concentration-dependent manner. These findings suggest that CCK-8S and cerulein activate intrinsic nitrergic nerves acting on CCK-1 receptors in order to cause relaxation of the rat duodenum longitudinal muscle.

Animals↗
PubMed1986

Prevention of recurrent ulcer bleeding, a multicentre study of the effect of ranitidine and trimipramine over one year.

Short term studies of the prevention of bleedings from peptic ulcers and erosions have been reported by a number of authors following treatment with antacids (1), H2-receptor blockers, cimetidine (2-15), a combination of cimetidine and tranexamic acid (16), cimetidine and somatostatin (17), cimetidine and sucralfate or secretion (18, 19, 20), cimetidine compared to antacid (21), and cimetidine compared to antacid and pirenzepine (22). The H2-blocker rantitidine has been compared to placebo (24, 25, 26). An uncontrolled study has been performed using proglumide (27), a controlled study with vasopressin (28) and with secretin versus somatostatin (28). In the studies with H2-receptor antagonists conflicting results have been obtained. No report has been published concerning the effect over more than a few days or weeks.

Dibenzazepines↗
PubMedDate not supplied

A study of stimuli operative in the release of antibodies in the rat intestine.

We describe here a series of experiments which have been undertaken in the course of several years to try and study secretory mechanisms operative in the release of antibodies in the lumen of the intestine. The results of our experiments suggest that there are a number of stimuli that are efficacious in eliciting antibody release in the lumen of the rat intestine. These include the peptide hormones cholecystokinin and substance P, and cholinergic agonists such as pilocarpine. The fact that food has a similar effect indicates that the stimulation of antibody release is a physiological process co-ordinated with the ingestion of foreign antigens. We have also shown that food mediates its effect by means of cholecystokinin. Cholecystokinin promotes the release of antibodies belonging to the IgA, IgG, IgM and IgE isotypes. There is reason to believe that not all the IgA is secretory IgA. Antibody release can be inhibited by the CCK antagonist proglumide and by cholinergic antagonists. The intracellular messengers that participate in this process are changes in cytosolic calcium. It is proposed that the release of antibodies in the gastrointestinal tract is an active secretory process.

Animals↗