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At least 307 records · Page 17Linked to original sources
PubMed1989

Effect of a new cholinergic agonist, aclatonium napadisilate, on exocrine and endocrine rat pancreas.

The effect of aclatonium napadisilate, a choline sulfonate derivative, on exocrine and endocrine pancreatic functions was compared with that of carbamylcholine in both isolated pancreatic acini and the isolated perfused pancreas of rats. In the isolated acini, aclatonium napadisilate and carbamylcholine stimulated amylase release. While the relative efficacy of aclatonium napadisilate was the same as that of carbamylcholine, aclatonium napadisilate was about 20-fold less potent. In the isolated perfused pancreas, 0.1 microM or higher concentrations of aclatonium napadisilate elicited a significant insulin release in the presence of 8.3 mM glucose, whereas an appreciable increase in pancreatic exocrine secretion was obtained with a 10 times higher concentration (1.0 microM). In contrast, carbamylcholine did not stimulate insulin release at a dose (0.1 microM) that stimulated pancreatic exocrine secretion. The insulin-releasing effect of aclatonium napadisilate depended on the glucose concentration. These stimulatory effects of aclatonium napadisilate on endocrine and exocrine pancreatic secretion were inhibited by the muscarinic receptor antagonist pirenzepine but were not affected by the cholecystokinin receptor antagonist proglumide. These results indicate that aclatonium napadisilate stimulates both endocrine and exocrine pancreatic secretion via muscarinic receptors and that its action on B cells is more potent than on the exocrine pancreas.

Acetylcholine↗
PubMed1989

Bombesin: an activator of specific Aeromonas antibody secretion in rat intestine.

The effect of bombesin (BBS) in modulating the secretion of specific Aeromonas antibodies in rat intestine was determined. Rats were immunized with the culture supernatant of Aeromonas hydrophila, isolate SSU. This culture supernatant contained a number of toxins that may be considered virulence factors. After 24 days of immunization, rats were anesthetized and a 10-cm intestinal segment was perfused with phosphate-buffered saline. The effluents were collected for measurement of IgA and IgG by the enzyme-linked immunosorbent assay. When compared with the effect of intravenous administration of normal saline in the control group, intravenous injection of BBS (20 micrograms/kg) in the experimental group caused a significant increase in rat intestinal IgA and IgG in perfusates. The stimulatory effects of BBS on the presence of IgA and IgG were depressed partially by proglumide, a receptor antagonist of cholecystokinin (CCK) and gastrin. Treatment with pentagastrin (250 micrograms/kg) accelerated intestinal secretion of IgA, but failed to stimulate intestinal IgG secretion. In addition, intravenous injection of CCK-8 (120 ng/kg) evoked the intestinal secretion of either IgA or IgG. These findings demonstrated that BBS, gastrin, and CCK can stimulate antibody secretion in rat intestine and the stimulatory effect of BBS may be mediated partially via release of CCK and gastrin. These results suggest that neuropeptides such as BBS and gastrointestinal hormones, eg, CCK and gastrin, may participate in the regulation of intestinal secretion of IgA and IgG antibodies, respectively, in rats.

Aeromonas↗
PubMed1990

Duodenal osmolality drives gallbladder emptying in humans.

The effect of duodenal osmoreceptor stimulation on gallbladder motility was evaluated in 18 normal subjects during intraduodenal infusion of 280, 560 and 840 mosm/liters NaCl solutions. Gallbladder emptying was found to be dose-dependent between 560 and 840 mosm/liter (P less than 0.01 vs basal volume). The effect of duodenal infusion of hypertonic saline on gallbladder emptying was prevented by atropine and partially antagonized by naloxone, indicating that cholinergic and endorphinergic pathways may be involved in regulating this reflex. Since proglumide, a cholecystokinin (CCK) antagonist, did not affect gallbladder emptying induced by hypertonic saline, it seems likely that CCK is not released by increasing duodenal osmolality. A significant reduction in gallbladder volume was obtained when hyperosmolar saline was delivered into the duodenum, whereas no emptying was seen when infused into the gastric antrum or the jejunum, suggesting that osmoreceptors that activate gallbladder emptying are located only in the duodenum. Additionally, all subjects manifested central symptoms (nausea or vomiting) during duodenal infusion of hypertonic saline, suggesting that central mechanisms might be activated by a change in duodenal osmolality. Our data indicate that the osmolality of duodenal contents might regulate gallbladder motility by neural atropine- and naloxone-sensitive pathways.

Adult↗
PubMed1989

Gastrointestinal hormone receptors on isolated smooth muscle cells from gastric antrum of the rabbit.

The regulation by gastrointestinal polypeptide hormones of contraction and relaxation of functionally isolated smooth muscle cells from gastric antrum of the rabbit has been investigated. Gastrin, cholecystokinin (CCK-8) and motilin induced a rapid contraction of isolated cells: significant response occurred within a 5-sec incubation with these peptides and maximal response (40% decrease in cell length) after 30 sec. A higher sensitivity of smooth muscle cells to gastrin and CCK-8 than to motilin stimulations was demonstrated (EC50 = 10 pM for both gastrin and CCK-8 and EC50 = 1 nM for motilin). The minimal gastrin fragment required to get full contraction was the C-terminal pentapeptide amide common to gastrin and CCK. Proglumide inhibited gastrin- or CCK-8- but not motilin-induced contractions with an IC50 of 50 microM. contraction induced by gastrin and motilin required normal levels of extracellular calcium, whereas that due to CCK-8 seemed to be independent of extracellular calcium. Vasoactive intestinal polypeptide (VIP) caused a relaxation of smooth muscle cells maximally contracted by carbachol or CCK-8 or gastrin (EC50 = 2.2 nM) with a parallel increase in intracellular cAMP content.

Animals↗
PubMed1984

Interactions of cholecystokinin octapeptide and dopamine on nucleus accumbens neurons.

Local microiontophoretic administration of cholecystokinin octapeptide (CCK) increased the firing rates of neurons in the dorsomedial nucleus accumbens (NAc), but exerted little to no effect on lateral NAc neurons. This regionally defined CCK-effect corresponds to the topographical distribution of CCK-like immunoreactive nerve terminal fiber networks and CCK receptors within the NAc. The excitatory effects of CCK were selectively antagonized by the CCK antagonist proglumide. Dopamine (DA) decreased the firing of NAc cells and reversed CCK-induced excitation. These results suggest that CCK and DA may interact to influence the activity of neurons within the dorsomedial NAc.

Animals↗
PubMed1987

Inhibition of synaptic transmission in the hippocampus by cholecystokinin (CCK) and its antagonism by a CCK analog (CCK27-33).

The actions of CCK-8 and putative CCK-8 antagonists were examined on synaptic transmission in the hippocampal slice preparation. CCK-8 (10(-7) M) caused a reversible depression of postsynaptic responses of the Schaffer collateral-CA1 synapse. CCK-mediated depression was unaffected by proglumide (10(-3) M) but was antagonized by a CCK analog (CCK27-33). The CCK analog alone had an excitatory effect on synaptic transmission. These results suggest that CCK has an inhibitory action on synaptic transmission.

Animals↗
PubMed1988

Attenuation of dark-induced hyperlocomotion by a cholecystokinin antagonist in the nucleus accumbens.

A dark-induced hyperlocomotion paradigm was developed to investigate the role of endogenous cholecystokinin in mediating exploratory locomotor activity in the mesolimbic pathway, where cholecystokinin coexists with dopamine. Microinjection of the cholecystokinin receptor antagonist, proglumide, 10-20 micrograms, into the medial posterior nucleus accumbens, significantly inhibited dark-induced hyperlocomotion, while having no effect on locomotion in the light. These data suggest that endogenous cholecystokinin contributes to behaviorally relevant functions of the activated mesolimbic pathway.

Animals↗
PubMed1990

Cholecystokinin octapeptide antagonized opioid analgesia mediated by mu- and kappa- but not delta-receptors in the spinal cord of the rat.

Intrathecal (ith) injection of cholecystokinin octapeptide (CCK-8) to the rat with single dose of 4 or 40 ng, or successive doses from 0.1 to 1 microgram at 10 min intervals produced neither analgesia nor hyperalgesia. However, the analgesia produced by ith injection of PL017, a specific mu-receptor agonist or 66A-078, a specific kappa-receptor agonist could be markedly antagonized by CCK-8 at a dose as small as 4 ng. In contrast, analgesia produced by ith injection of delta-agonist DPDPE could not be blocked by CCK-8 even at a dose as high as 40 ng. Since the effect of CCK-8 could be totally reversed by the CCK receptor antagonist proglumide, this effect is most probably mediated by CCK receptors.

Animals↗
PubMed1991

Electrophysiological evidence of modulatory interaction between dopamine and cholecystokinin in the nucleus accumbens.

Dopamine has been shown to modulate responses of accumbens neurones to excitatory inputs from the amygdala. The demonstration that cholecystokinin (CCK) co-exists and appears to be co-released with dopamine in the accumbens suggests that the modulatory action of dopamine in the accumbens may in turn be modified by CCK. This possibility was investigated in the present study. Single unit recordings were obtained in the medial and caudal accumbens of urethane-anaesthetized rats. These neurones were strongly excited by amygdala stimulation, and concurrent stimulation of the ventral tegmental area (VTA) at 10 Hz attenuated the responses, presumably due to dopamine release. Iontophoretic application of proglumide (PRG) at 30 nA enhanced the attenuating effect of VTA stimulation on the excitatory response to amygdala stimulation. Exogenous dopamine produced a similar attenuation in response and the attenuation was in turn suppressed by concurrent iontophoresis of sulphated CCK fragments applied at a current titrated not to produce significant effect on the spontaneous activity of the neurone nor its response to amygdala stimulation. These results demonstrate that exogenous and endogenous CCK can modify the postsynaptic action of dopamine in the nucleus accumbens in addition to modulating its release shown in other studies, and further suggests that CCK is likely an endogenous functional antagonist of dopamine, serving a comodulatory role in regulating synaptic transmission in the ventral striatum.

Amygdala↗
PubMed1992

Cholecystokinin antagonists inhibit in vivo voltammetric signals generated by KCl-induced slow wave depolarization in rat caudate.

The effect of sulfated cholecystokinin octapeptide (CCK-8S) on the generation of slow wave depolarisation in the rat caudate-putamen (CPu) was studied using in vivo voltammetry. Pressure-ejection of 50 microM CCK-8S into the CPu induced voltammetric signals recorded at widely spaced Nafion-coated carbon fiber microelectrodes. Based on the in vitro selectivity properties of the electrodes, the signals were predominantly due to increases in extracellular concentrations of dopamine (DA). The similar propagation rates of the signals induced by CCK-8S and 100 mM KCl suggests that the CCK-8S-induced signals represent a slow wave depolarization (SWD). Since the CPu was refractory to a second CCK-8S stimulus, the effects of CCK antagonists on DA signals associated with 100 mM KCl-induced SWD were evaluated. Proglumide (4-64 mg/kg) and lorglumide (20-640 micrograms/kg), administered intravenously, decreased KCl-induced DA signals in the CPu in a dose-dependent manner. The antagonistic effect of lorglumide on the KCl-induced signals was partly reversed 130 min after drug administration. The generation of a SWD by CCK-8S and the inhibitory effects of CCK-8S antagonists on KCl-induced signals suggest that the susceptibility of the CPu to KCl-induced SWD may be enhanced by CCK-8S.

Animals↗
PubMed1992

Ceruletide, a CCK-like peptide, attenuates dopamine release from the rat striatum via a central site of action.

Ceruletide (CLT), a cholecystokinin-like peptide was given subcutaneously or via the perfusate to rats to clarify the site of action (peripheral vs. central location) of CLT, using in vivo microdialysis techniques. Striatal dopamine (DA) release induced by haloperidol (HPD) was significantly inhibited by subcutaneously administered CLT (160 micrograms/kg) when given with a perfusate containing 15 mM K+. Subdiaphragmatic vagotomies failed to block the inhibitory effect of CLT. CLT (10(-15)-10(-11) M) locally applied, via a dialysis tube, produced an inhibitory effect on HPD-induced DA release in the striatum in a dose-dependent manner. The inhibitory effect of CLT given subcutaneously on DA release was antagonized by both locally applied proglumide and systemically administered L-365,260. These findings suggest that systemically administered CLT can directly act on the striatal neurons via CCK-B receptors and produce an inhibitory effect on DA release in the striatum under appropriate depolarization.

Animals↗
PubMed1989

The behavioral effects of CCK8 injected into the medial nucleus accumbens are dependent on the motivational state of the rat.

The effects of CCK8 injected into the rat median nucleus accumbens on exploration and locomotion were measured in the four hole box and open-field tests. CCK8 (1 fmol to 100 pmol) induced hypoexploration in the four hole box (duration, frequency), with the pattern of the responses remaining unchanged compared to those of the control group. These effects were reversed by injection of the CCK antagonist proglumide (20 micrograms) into the nucleus accumbens. In the open-field test, CCK8 (100 pmol) only decreased locomotion and rearing when the rats were not habituated to the environment. These results show that the behavior of rats exposed to a novel external stimuli is highly sensitive to CCK8.

Animals↗
PubMed1995

Stimulatory effect of muscimol on gastric acid secretion stimulated by secretagogues in vagotomized rats under anesthesia.

The effect of intravenous administration of muscimol, a GABAA receptor agonist, on gastric acid secretion from perfused stomach was studied in vagotomized rats anesthetized with urethane. Muscimol did not stimulate acid secretion by itself. In contrast, muscimol dose dependently potentiated acid secretion induced by pentagastrin, bethanechol and direct vagal stimulation, but not histamine. Muscimol-potentiated acid secretion induced by pentagastrin and bethanechol was not influenced by pretreatment with atropine or cimetidine, respectively. Muscimol-potentiated acid secretion evoked by direct vagal stimulation was prevented by pretreatment with proglumide, a gastrin receptor antagonist. Muscimol-potentiated acid secretion evoked by bethanechol was dose dependently prevented by bicuculline methiodide, suggesting an involvement of peripheral GABAA receptors. These results suggest that muscimol stimulates acid secretion under certain conditions, and that two mechanisms are involved in this effect. The effects of muscimol on acid secretion may be mediated by increasing the release of histamine by pentagastrin, bethanechol and direct vagal stimulation. In addition, muscimol would also be effective if muscarinic agents were already occupying muscarinic acetylcholine receptors on parietal cells.

Anesthesia↗
PubMed1986

Structure-activity relationship of subtypes of cholecystokinin receptors in the cat lower esophageal sphincter.

Cholecystokinin (CCK) causes relaxation of the cat lower esophageal sphincter (LES) by stimulating CCK receptors on the noncholinergic, nonadrenergic inhibitory neurons and causes contraction by stimulating CCK receptors on the sphincter muscle. Studies were performed in anesthetized cats to identify differences between the two CCK receptors by investigating the structure-activity relationships of various fragments of CCK or gastrin molecule. Lower esophageal sphincter pressures were monitored continuously, using continuously perfused catheters, and agents were administered intravenously or close intraarterially. Based on their doses and the presence or absence of tetrodotoxin pretreatment, CCK analogues produced either relaxation or contraction of the sphincter. The relative potencies of CCK analogues on the inhibitory (neural) response were CCK-8 greater than G-17-I greater than or equal to dCCK greater than CCK-4(1:1/14,000: 1/15,000: 1/335,000). Sulfated gastrin was nearly as potent as CCK-8. The relative potency of these agents on the contractile (muscle) response was CCK-8 = G-17-I greater than or equal to dCCK-8 greater than CCK-4 (1:1:1/4.5: 1/2000). Deamidated CCK-8 was inactive. Proglumide shifted the dose-response curves of the inhibitory as well as excitatory effects of CCK analogues to the right. These studies show that there are two distinct species of CCK receptors: (a) The CCK alpha receptors, present on the inhibitory neurons, are very discriminative and are critically dependent on SO4; and (b) the CCK beta receptors, present on the sphincter muscle, are not discriminative and are not critically dependent on SO4. Nonsulfated gastrin may share the CCK beta receptors with CCK.

Animals↗
PubMed1987

Effect of cholecystokinin and of its antagonist, of atropine, and of food on the release of immunoglobulin A and immunoglobulin G specific antibodies in the rat intestine.

Cholecystokinin has previously been shown to produce a rise in immunoglobulin A (IgA) antibodies in the intestinal fluid of human volunteers. Whether the source of these antibodies was pancreatic, biliary, or mucosal had not been defined. The object of the present investigation was to study factors involved in regulating the release of IgA and IgG antibodies from the intestinal mucosa. Hooded-Lister rats were sensitized to ovalbumin. After the sensitization protocol, which lasted 21 days, the rats were anesthetized and a segment of intestine 10 cm long was isolated and perfused in vivo. This segment was flushed with normal saline for 30 min to remove all pancreatic, biliary, and other secretions. It was found in this model that after the intravenous injection of cholecystokinin-octapeptide there was a rise of IgA and IgG antibodies within 2.5 min. Significantly increased secretion of IgA lasted for 10 min, and increased secretion of IgG lasted for 20 min. The cholecystokinin antagonist proglumide reduced the secretions of both immunoglobulins. Atropine reduced baseline IgA secretion by one-half. Intragastric protein hydrolysate, which left the body through the severed end of the duodenum, also raised IgA and IgG levels significantly in the perfused intestine. Control animals receiving intragastric normal saline did not have an elevation of IgA or IgG levels. The phenomena described here demonstrate that the rate of IgA release from the mucosa is influenced by endocrine and nervous stimuli. The rate of IgG release is, as far as could be ascertained, only under endocrine control and not significantly influenced by the cholinergic antagonist atropine.

Animals↗
PubMed1991

Neuromodulation of guinea pig intestinal electrolyte transport by cholecystokinin octapeptide.

We examined the effect of cholecystokinin octapeptide on electrolyte transport across isolated guinea pig mucosa. Segments of distal ileum stripped of longitudinal muscle and bathed on both sides with a Krebs'-bicarbonate buffer responded to cholecystokinin octapeptide when studied under short-circuited conditions. Cholecystokinin octapeptide (0.5-50 nmol/L) evoked a transient (4-10-minute) increase in transepithelial potential difference and short-circuit current upon application to the serosal side. Maximal increases in short-circuit current, achieved at 50-500 nmol/L, were 67 +/- 11 microA/cm2, whereas half-maximal effects occurred at a concentration of 0.7 +/- 0.2 nmol/L. Pretreatment of the tissues with 0.5 mumol/L atropine reduced the maximal short-circuit response to cholecystokinin octapeptide by 53%. The change in short-circuit current due to cholecystokinin octapeptide was nearly abolished by pretreatment with 0.5 mumol/L tetrodotoxin, suggesting neuronal involvement. Cholecystokinin octapeptide-induced increases in short-circuit current were halved by removal of serosal buffer Ca2+ and were abolished in Cl(-)- and HCO3(-)-free buffer. The cholecystokin-receptor antagonists proglumide and lorglumide shifted the concentration-response curve for cholecystokinin octapeptide competitively to the right, having antagonists potencies of 130 and 0.03 mumol/L, respectively. Cerulein (0.1-500 nmol/L) also increased short-circuit current, whereas nonsulfated cholecystokinin octapeptide was ineffective. In conclusion, cholecystokinin octapeptide seems to act at neuronal cholecystokinin receptors to stimulate mucosal anion secretion, in part, by releasing acetylcholine.

Animals↗
PubMed1985

Cholecystokinin receptor mediated hydrolysis of inositol phospholipids in guinea pig gastric glands.

CCK-octapeptide (CCK-8) (EC50 = 0.5 nM), in the presence of Li+, increased 3H-inositol phosphate (IP) accumulation in guinea pig gastric glands prelabeled with 3H-inositol. CCK-8 desulfate, human gastrin I and pentagastrin were much less potent than CCK-8. Antagonists of CCK receptors such as proglumide, dibutyryl-c-GMP and CBZ-Tyr (SO3H)-Met-Gly-Trp-Met-AspNH2 shifted the CCK dose response curve to the right. However, histamine (H1 and H2), cholinergic, substance P and alpha- and beta-adrenergic receptor antagonists had no effect on 3H-IP accumulation induced by CCK. The results suggest that CCK receptor activation in gastric glands leads to an enhanced breakdown of inositol phospholipids which may relate to calcium mobilization and pepsinogen secretion.

Animals↗
PubMed1984

Effect of cholecystokinin octapeptide and ceruletide on release of acetylcholine from cerebral cortex of the rat in vivo.

The effect of cholecystokinin octapeptide (CCK-8) and its analogue, ceruletide on release of acetylcholine (ACh) from the cerebral cortex was investigated in urethane-anaesthetized and in unanaesthetized rats. Cholecystokinin octapeptide and ceruletide markedly stimulated output of ACh at doses of 1.5 and 5.0 micrograms/kg (i.p.), respectively. This effect was prevented by proglumide (160 mg/kg i.p.), a specific cholecystokinin receptor antagonist. At doses of 10 micrograms/kg (i.p.) and more, both CCK-8 and ceruletide decreased output of ACh from the cerebral cortex. The decrease was prevented by naloxone (1 mg/kg, s.c.), and replaced by a short-lasting increase. Cholecystokinin octapeptide and ceruletide appear therefore to affect the activity of cortical cholinergic fibres by acting upon both specific and opiate receptors. The interaction between CCK-8 and ceruletide, and opiate receptors either direct or through the release of endogenous opiates, was also demonstrated by the antagonism between ceruletide (1, 5 and 10 micrograms/kg, i.p.) and analgesia induced by morphine (5 mg/kg, s.c.), evaluated by the tail-flick test in the rat.

Acetylcholine↗