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[Stimulation of cholinergic receptors and changes in cyclic nucleotide levels in the cerebral cortex of the guinea pig].

The effect of Atropine and Physostigmine on 3'5' AMP and 3'5' GMP content was investigated in slices of guinea-pig cerebral cortex maintained at rest or electrically-stimulated. Atropine and Physostigmine did not modify either the basal content or the electrically-evoked increase of 3'5' AMP and 3'5' GMP. On the contrary, Betanechol 25 micro M significantly increased 3'5' GMP and 3'5' AMP content in slices kept at rest. The effect was abolished by Atropine 1,5 x 10(-7) M and d-tubocurarine 7 x 10(-6) M, respectively.

Animals↗

Cyclic adenosine monophosphate stimulates active potassium secretion in the rat colon.

To determine whether cyclic adenosine monophosphate influences active potassium transport in the rat colon, we studied the effect of dibutyryl cyclic adenosine monophosphate and theophylline on unidirectional transmural 42K fluxes across proximal colonic mucosa under short-circuited conditions. Active potassium secretion (-0.19 +/- 0.02 microEq/h X cm2) was present in animals maintained on a normal potassium diet. Both 0.5 mM dibutyryl cyclic adenosine monophosphate and 5 mM theophylline significantly increased net potassium secretion by 0.49 +/- 0.04 and 0.33 +/- 0.03 microEq/h X cm2, p less than 0.001, respectively; the stimulation of net potassium secretion was secondary to an increase in serosal-to-mucosal potassium transport without change in mucosal-to-serosal potassium movement. A similar increase in active potassium secretion (from -0.15 +/- 0.03 to -0.32 +/- 0.03 microEq/h X cm2, p less than 0.005) was produced by bethanechol, a cholinergic muscarinic agonist that alters sodium and chloride transport by a noncyclic adenosine monophosphate, calcium-dependent process. In animals maintained on a high potassium diet, active potassium secretion was significantly increased to -0.79 +/- 0.17 microEq/h X cm2 (p less than 0.001). In these potassium-loaded animals, theophylline produced a greater increase in active potassium secretion (0.91 +/- 0.10 vs. 0.33 +/- 0.03 microEq/h X cm2, p less than 0.001) than in animals fed a normal potassium diet. These studies demonstrate that cyclic adenosine monophosphate and noncyclic adenosine monophosphate mediated secretogogues stimulate active potassium secretion. We speculate that the mechanism by which cyclic adenosine monophosphate increases active potassium secretion is related to an increase in luminal potassium conductance.

Animals↗

Effects of the sympathetic nervous system on bethanechol-induced elevation of gastric acid secretion and mucosal blood flow in rats.

Effects of stimulation of the sympathetic nervous system on the bethanechol-induced increase in gastric acid secretion and mucosal blood flow (MBF) were studied in anesthetized, gastric fistula rats. The gastric acid secretion and MBF were increased by i.v. infusion of a supramaximal dose of bethanechol (10.0 micrograms/kg/min). The bethanechol-induced gastric acid secretion was abolished by administration of atropine (0.1 mg/kg i.v.), but was not influenced by hexamethonium (2.0 mg/kg i.v.) in the dose which abolished the gastric acid secretion induced by vagus nerve stimulation. Stimulation of the splanchnic postganglionic (SP) nerve or infusion of norepinephrine was carried out under the steady, increased state of acid secretion and MBF. Stimulation of the SP nerve significantly reduced the gastric acid secretion but the MBF was little affected. Thus, the delta MBF/delta H+ ratio was significantly increased during this stimulation. Intravenous infusion of norepinephrine also reduced the acid secretion without affecting the MBF. The delta MBF/delta H+ ratio was also significantly increased during infusion of norepinephrine. Phentolamine, but not propranolol, abolished the inhibitory effects of SP nerve stimulation and infusion of norepinephrine on the gastric acid secretion. These results suggest that the SP nerve acts on the structures peripheral to the postganglionic parasympathetic nerve terminals and directly inhibits the parasympathetically stimulated gastric acid secretion through alpha adrenoceptors, independently of changes in the gastric MBF in rats.

Animals↗

Inhibition of acid secretion in the rat isolated stomach preparation by 5-hydroxytryptamine.

The effect of 5 hydroxytryptamine (5-HT) on gastric acid secretion by the rat isolated stomach has been studied. 5-HT (10 microM) significantly inhibited secretory responses to pentagastrin, histamine and isoprenaline but not those due to bethanechol, dibutyryl cyclic AMP or a phosphodiesterase inhibitor. The response was antagonized by methysergide (25 microM), indomethacin (28 microM) and ibuprofen (240 microM) but not by TTX (1 microM). It is concluded that 5-HT can exert a direct, inhibitory effect on acid secretion by the rat stomach and that this may involve the products of cyclo-oxygenase activity.

Animals↗

Facilitation of ganglionic response to bethanechol by repetitive stimulation of the preganglionic nerve.

Repetitive stimulation of the preganglionic nerve of the rat superior cervical sympathetic ganglion potentiates the amplitude of asynchronous firing elicited by the muscarinic agonist, bethanechol. The amplitude of stimulus-induced facilitation is not related to frequency of stimulation and occurs with a stimulation frequency of 10 Hz or greater. Facilitation, but not the asynchronous firing is reduced by lowering the temperature of the bathing solution. Dibutryl cyclic adenosine monophosphate and theophylline had no effect on asynchronous firing but reduced stimulus-induced facilitation. Neither dibutryl cyclic guanosine monophosphate up to 1 mM nor nitroprusside had any significant effect on bethanechol-induced asynchronous firing or stimulus-induced facilitation. Tetraethylammonium caused a 200% increase in stimulus-induced facilitation. Acetylcholine, in a concentration that elicited maximum nicotinic firing, had no effect on the magnitude of bethanechol-induced asynchronous firing. Increased Ca++, Mg++ or Mn++ reduced both asynchronous firing and stimulus-induced facilitation. It is concluded that facilitation is a result of transmitter release, possibly not acetylcholine.

Acetylcholine↗

Electrical activity of the opossum lower esophageal sphincter in vivo. Its role in the basal sphincter pressure.

Studies were performed in anesthetized opossums to investigate the electrical activity that may characterize the lower esophageal sphincter. The stomach and lower end of the esophagus were immobilized on a specially prepared stage to eliminate movement artifacts. Extracellular electrical activity was recorded with bipolar needle electrodes. The sphincter pressure was measured with a continuously perfused catheter system. The lower esophageal sphincter showed continuous spike activity with or without phasic variations in their occurrence. The usual frequency of the spikes was 20 to 50 per min, and their duration was 81.2 +/- 8.9 msec (mean +/- SE). The spike potentials ceased with esophageal distention, which also caused a fall in the sphincter pressure. The spikes were abolished by isoproterenol and they increased with bethanechol. Correlation of the spike activity with the pressure revealed that the sphincter pressure was higher when the spike potentials were present, but a major part of the pressure existed in the absence of any spike activity. These studies show that: (1) the oppossum lower esophageal sphincter is characterized by continuous spike potentials, and (2) the major fraction of the basal pressure is, however, independent of the spike potentials.

Animals↗

[Sucralfate (Ulcogant). The mechanism of action of a cytoprotective agent].

The new antiulcer drug sucralfate is characterized by a multiple mode of action. Its predominant feature is a protection of the mucosa from endogenous and exogenous noxious agents. These cytoprotective properties result from a locally formed layer covering ulcers and erosions which inhibits the diffusion of H-ions and pepsin to the damaged mucosa. This layer is also stable against exogenous substances with deleterious effects on the mucosa like alcohol and salicylates. Furthermore, sucralfate binds pepsin and bile acids. Recently, a stimulating effect of sucralfate on the release of prostaglandins and the regeneration of epithelial cells in the gastric mucosa was demonstrated. There is no influence of sucralfate on the production of gastric juice and pH. Since sucralfate is minimally absorbed it is a safe and well tolerated drug.

Adsorption↗

A method for studying the actions of drugs on motility of vascularly perfused segments of human colon.

The isolated, vascularly perfused human colon is a novel method for investigating drug action on this organ. Measurement of the integrated motility of the muscle layers and the facility for administering drugs via the blood supply represent advances over muscle strip studies. Viability of the specimens was improved by addition of Dextran 70 to the perfusion fluid to minimise oedema. Changes in motility were recorded with small, water-filled intraluminal balloons. Measurements were made for 10 min periods immediately before and after drug administration using a linear displacement method. Both neostigmine (1.0-3.0 micrograms/ml) and bethanechol (1.0-5 micrograms/ml) significantly increased motility of the segments, while morphine (10-50 micrograms/ml) did not.

Bethanechol Compounds↗

Repeated I. V. injections of calcium salts give rise to increased exocrine pancreatic cell sensitivity to caerulein and urecholine in the dog.

The persisting modifications induced by repeated intravenous infusion of calcium salts were investigated in five dogs with Thomas fistulae. Five control dogs were also tested. In calcium treated dogs the pancreatic secretion stimulated by graded doses of either caerulein or urecholine showed: a) an increase in the sensitivity of acinar cells to caerulein and urecholine and potentiation by caerulein of the water and bicarbonate response to secretin, in contrast to the decreased sensitivity to secretin alone reported previously. b) an inhibition of water and bicarbonate secretion with urecholine stimulation, c) an inhibition of calcium secretion which was significant with caerulein. These findings could explain the data previously observed on basal pancreatic secretion of calcium treated dogs such as protein hypersecretion with protein precipitates and reduced bicarbonate secretion which are similar to modifications observed in chronic alcoholic dogs and men. These results have a clinical relevance to the understanding of the pathology of chronic pancreatitis.

Animals↗

[Vesicourethral physiology during continence and urination in cats. In vivo and in vitro studies].

The mechanisms implicated in the opening of the bladder neck during voiding are still controversial. We present a study of the reflexes of bladder, urethra and periurethral striated muscles in the cat. The study in vivo shows that a passive muscle tonus of the urethra is able to maintain the continence. During voiding, opening of the bladder outlet is done actively: contraction of the longitudinal and relaxation of the circular muscle layers of the urethra associated with detrusor contraction. There is a local reflex between the urethra, bladder and periurethral striated muscles that completes emptying of the bladder with an interrupted stream. The study in vitro confirms that the 2 muscle layers of the urethra have different innervation: the parasympathomimetic agents act on the longitudinal layer and very weakly on the circular. Both layers react to adrenergic stimulation.

Animals↗

Effects of omeprazole, a substituted benzimidazole, on gastrointestinal secretions, serum gastrin, and gastric mucosal blood flow in dogs.

In dogs with gastric fistulas and vagally denervated Heidenhain pouches, omeprazole, a benzimidazole derivative infused intravenously or given intraduodenally, dose-dependently inhibited gastric acid secretion, which had been induced by histamine, pentagastrin, or urecholine. It also suppressed gastric acid response to physiologic stimulants such as sham-feeding and gastric peptone meal without affecting serum gastrin level. The inhibition of histamine-induced acid secretion was accompanied by a parallel reduction in the mucosal blood flow, but no significant alteration in the ratio (R) value, indicating that omeprazole primarily affected gastric acid secretion but did not limit gastric mucosal microcirculation. Omeprazole, infused into the Heidenhain pouch, caused a dose-dependent inhibition of the Heidenhain pouch response to intravenous histamine without any significant change in the acid response of the main stomach and plasma concentrations of the drug. This indicates that omeprazole may exhibit local inhibitory action on the oxyntic glands. Omeprazole did not affect gastric mucosal integrity or the rate of alkaline secretion from the gastroduodenal mucosa or the pancreas stimulated by duodenal acidification or secretin.

Administration, Topical↗