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Biomedical subjects

G Bertaccini

Publications and source records attributed to G Bertaccini.

At least 127 records · Page 7Linked to original sources
PubMed1983

Cardiac effects of the new H2-receptor antagonists.

A series of new H2-receptor antagonists were tested for their effects on different isolated heart preparations. In the guinea-pig atria and papillary muscle the inhibitory effect on histamine H2-receptors was evaluated. In the perfused rabbit heart and in strips of human atria the effect of the H2-antagonists on the spontaneous or electrically-stimulated contractions was evaluated. In the first two preparations some main quantitative differences were pointed out, tiotidine and compound SKF 93479 being the most potent antagonists, cimetidine, metiamide and ranitidine the less effective. In the rabbit heart and in human atria results were quite different: cimetidine and ranitidine were virtually ineffective up to the maximum concentration tested (3 x 10(-3) M), oxmetidine and compound SKF 93479 had a negative inotropic and chronotropic effect starting from concentrations of 3 x 10(-6)-10(-5) M. On the basis of the behaviour of other compounds endowed with negative cardiac effects (propranolol, anaesthetic-like compounds, verapamil) and of that of compounds capable of counteracting the effect of oxmetidine (increased concentration of calcium ions and isoproterenol) it was hypothesized that oxmetidine may interfere in the transport of calcium ions. Our data emphasize the importance of the different structure of the H2-antagonists in determining non-specific effects absolutely independent of the primary action that is the H2-receptor blockade.

Animals↗
PubMed1983

Action of angiotensin on vascular and intestinal smooth muscle and its antagonism by saralasin.

Angiotensin II was tested for its activity on rabbit aorta, lower esophageal sphincter (LES) from the rat, rat gastric fundus and rat colon. The peptide had a powerful stimulatory effect on vascular and extravascular smooth muscle beginning from concentrations of 10(-10) M. Its effect was antagonized by saralasin which acted in the different preparations to approximately the same extent: active concentrations of saralasin varied from 10(-8) M to 10(-7) M. The activity of angiotensin on the rabbit aorta appeared to be a direct one on its specific receptors. A mixed action connected with stimulation of adrenergic alpha receptors was observed in the rat LES, whereas an interference of the prostaglandin system was pointed out in the rat fundus and the rat colon. The circumstance of a similar sensitivity of the various tissues to the stimulatory effect of angiotensin and a similar degree of antagonism induced by saralasin tends to minimize the hypothesis of different subtypes of angiotensin receptors at least under the conditions of the present investigation.

Angiotensin II↗
PubMed1983

Histamine receptors in the human ureter.

The occurrence of histamine H1- and H2-receptors in the human ureter was studied by means of relatively selective agonists and antagonists of both kinds of receptors. Isolated preparations of small strips of human ureters removed during surgery were used. Histamine and the H1-agonist 2-aminoethylthiazole contracted the ureter in a dose-dependent fashion whereas the H2-agonists dimaprit and impromidine were ineffective. The H1-antagonist chlorpheniramine shifted to the right the dose-response curves to histamine and to 2-aminoethylthiazole with the kinetics of the competitive antagonism. Conversely the H2-antagonists cimetidine, metiamide and tiotidine potentiated the effect of histamine by a factor of 3 though high concentrations had to be used (25 - 30 micrograms/ml). Both H1 and H2-antagonists were not able to modify the basal tone and/or motility showed by ureteral strips. All the above data suggested that H1-receptors are predominant in the human ureteral muscle and the contraction induced by their stimulation completely mask the effect of the H2-receptors stimulation. Since H2-agonists were ineffective in basal conditions and H2-antagonists potentiated the effect of histamine which is spasmogenic, we may suggest that H2-receptors are less numerous than H1-receptors and their stimulation cause a slight relaxation of the ureteral muscle. This situation is not uncommon in other smooth muscle system (e.g. respiratory system and gastrointestinal tract).

Chlorpheniramine↗
PubMed1983

Extragastric H2-receptors.

The discovery of H2-receptors by Black and coworkers opened a new era in the history of histaminology. Their importance became apparent when, soon after their discovery, the physiological role of histamine in the regulation of gastric secretion was clarified. In the last decade the explosion of research in the field of histamine and its receptors has demonstrated that H2-receptors have a much wider distribution than previously suspected. H2-receptors are found in the brain, the endocrine and exocrine glands, the pulmonary system, the cardiovascular system of different species, the gastrointestinal muscle, the genitourinary system, the immunological system and in the skin. In some instances stimulation of the various H2-receptors evokes responses that are opposite to those elicited by stimulation of H1-receptors. In other cases they are quite similar. Usually, activation of H2-receptors leads to an increased activity of the adenylate cyclase system with a consequent increase in intracellular cyclic AMP. Most H2-receptors are located postsynaptically on muscle or gland surfaces. However, there is recent evidence concerning the possibility of a presynaptic localization with a modulatory function on the release of different mediators. Finally, controversy exists over the possibility that H2-receptors do not represent a homogeneous population. In fact, several observations suggest that "anomalous" H2-receptors are characterized by different sensitivity to the H2-antagonists and/or antagonists in various tissues. If this is true, exact characterization of H2-receptors will be decidedly more difficult and will require "super selective" H2-agonists and antagonists which are not currently available.

Animals↗
PubMed1983

Evidence against the temperature-dependent interconversion of histamine H1- and H2-receptors in the guinea-pig ileum.

1 The possible temperature-dependent interconversion of histamine H1- and H2-receptors in the guinea-pig ileum suggested from previous studies was re-investigated by use of new and selective H2-receptor agonists and antagonists. 2 Chlorpheniramine, and H1-blocker, caused a rightward shift of the cumulative histamine dose-response curve at both 37 degrees C and 12 degrees C. Conversely cimetidine and tiotidine, two H2-receptor blockers, were ineffective at both temperatures. Metiamide behaved as a non competitive antagonist at 12 degrees C but only in very high concentrations. 3 Dimaprit and impromidine, two selective H2-receptor agonists, were inactive at both 37 degrees C and 12 degrees C when given alone, whereas at both temperatures they elicited the already described relaxation of the contractions induced by histamine. 4 Similar results were obtained on the guinea-pig whole ileum and on the longitudinal muscle strip: this indicates a lack of interference of the circular smooth muscle. 5 Our results allow us to conclude that no temperature-dependent interconversion of histamine H1- and H2-receptors occurs in the guinea-pig ileum.

Animals↗
PubMed1983

Further observations on the motor activity of some new histamine H2-receptor antagonists on the digestive system.

Some new H2-receptor antagonists were tested for their motor effects on the rat lower oesophageal sphincter, on the guinea pig ileum and on the guinea pig gall bladder. Two of these compounds, SKF93479 and DA4577, were found to be virtually inactive despite the fact that they are the most potent antagonists of the H2-receptors so far described. Ranitidine possessed a stimulatory effect on all the preparations examined and its mechanism of action was shown to involve the cholinergic system. Conversely oxmetidine exerted an inhibitory effect on the contractions produced by a variety of spasmogenic compounds. All of these observations, together with other data from our laboratory, seem to suggest that H2-receptors do not play an important role in the regulation of the motility of the digestive system. Moreover our data emphasize the fact that the motor effects of the H2-antagonists are connected with single molecules rather than with the entire class, and therefore represent side-effects of these compounds independent of the H2-receptor blockade.

Acetylcholine↗
PubMed1983

Pirenzepine and exocrine secretions: a selective agent for gastric glands?

Nineteen healthy volunteers were studied to investigate whether or not muscarinic receptors of different exocrine glands could be distinguished from one another by the use of pirenzepine. A simultaneous evaluation of lacrimation, salivation and gastric secretion was carried out, bethanechol (80 micrograms/kg/hr) being used as a stimulant and pirenzepine (10 or 5 mg i.v.) as an inhibitor. Bethanechol increased salivation significantly and the volume of gastric juice, and non-significantly increased lacrimation and total acid output. Pirenzepine abolished the hypersecretion induced by bethanechol, and decreased the basal level of the exocrine secretions, to approximately the same extent. These experiments seem to demonstrate that if there is a difference among the muscarinic receptors of lacrimal, salivary and gastric oxyntic glands, pirenzepine is unable to discriminate them from one another, at least under the experimental conditions of this investigation.

Adult↗
PubMed1983

[Protective effect of ranitidine in acute experimental pancreatitis in the rat].

Acute experimental pancreatitis was induced in rats, with a polyethylene splint placed into the duodenum, by the closed duodenal loop technique. Ranitidine (20 mg . kg-1) or saline were administered intraperitoneally every 8 hrs, beginning 15 min prior to surgery. The degree of pancreatitis and the amylase to creatinine clearance ratio (ACCR) were evaluated in all the animals after sacrifice. Ranitidine-treated animals showed significant by reduced pancreatic damage and ACCR values in comparison with non-treated rats. These data confirm the efficacy of ranitidine as a preventive agent in the development of acute pancreatitis and suggest that controlled trials should be performed with this H2-antagonist in the human subyects with this disease.

Acute Disease↗
PubMed1983

Action of MDL 646, a new synthetic prostaglandin, on gastric acid secretion of some experimental animals.

The new synthetic prostaglandin 11,15-dihydroxy-16-methyl-16-methoxy-9-oxo-prost-13-en-1-oic acid,methyl ester (8 alpha,11 alpha,15R,16R) (compound marked MDL 646), belonging to the 16-methyl-16-methoxy series, was tested for its activity on gastric secretion of different animal species and in different experimental conditions. In the dog provided with gastric fistula and Heidenhain pouch, MDL 646 (25 micrograms/kg by intragastric administration) caused a remarkable inhibition of the histamine- and bethanechol-induced acid secretion, an effect which was more evident in the main stomach than on the Heidenhain pouch. In the cat, but not in the dog, the compound inhibited not only the hypersecretion induced by histamine and bethanechol but also that induced by pentagastrin. However, in this case, high doses (50-100 micrograms/kg) had to be used to obtain a significant inhibition. Similar results were obtained with the perfused stomach of the anaesthetized rat in which the natural PGE2 appeared to be from 3 to 5 times less potent. In the conscious rat provided with gastric fistula MDL 646 (15 and 50 micrograms/kg) significantly inhibited spontaneous gastric secretion. Untoward reactions, represented by salivation and vomiting lasting 30 min, were experienced by some dogs following administration of 50-100 micrograms/kg of the synthetic prostaglandin. These data appear of considerable interest in view of the possibility of the use of MDL 646 also in humans.

Alprostadil↗
PubMed1983

Inhibition of gastric emptying by angiotensin in the rat and its antagonism by saralasin.

Angiotensin, administered by intraperitoneal route (0.1 - 100 micrograms/kg) significantly delayed gastric emptying in the conscious rat. This action, most probably connected with the spasmogenic effect on the gastroduodenal junction, was antagonized by saralasin (125 and 250 micrograms/kg intraperitoneally). Our data seem to suggest an action of the peptide on the stomach mediated through an interaction with specific receptors.

Angiotensins↗
PubMed1983

Effect of MDL 646, a new synthetic prostaglandin, on gastroesophageal motility of the rat.

Compound marked MDL 646, a synthetic prostaglandin belonging to the 16-methyl-16-methoxy PGE1 series was tested for its motor effects on some in vitro and in vivo preparations from the rat. The lower esophageal sphincter (LES) was contracted at threshold doses ranging from 10 to 20 ng/ml; the fundus was even more sensitive whereas the pyloric sphincter showed remarkable differences according to the in vitro or in vivo preparation. In all the different tests MDL 646 showed a high degree of tachyphylaxis. PGE1 tested for comparison, exerted a constant relaxant effect in all the preparations excepting the gastric fundus. The present data emphasize the importance of the substitutions in positions 15 and 16 in the synthetic prostaglandin for determining the peculiar biological activity: in fact both MDL 646 and the parent PGE1 inhibit gastric secretion but they have almost opposite effects on gastroesophageal motility.

Alprostadil↗
PubMed1982

Different effects of the H2-antagonists on gastric emptying in the rat.

H2-receptor antagonists, in doses capable of inhibiting gastric secretion, did not generally affect gastric emptying. Exceptions were burimamide, which delayed the emptying rate, and ranitidine, which accelerated it. At higher doses burimamide, metiamide cimetidine and oxmetidine delayed gastric emptying, but ranitidine accelerated it to a greater extent. Tiotidine remained ineffective. These data suggest that changes in emptying rate are independent of the H2-receptor blockade.

Animals↗
PubMed1982

Histamine receptors in the lower esophageal sphincter (LES).

The motor response of histamine on the lower esophageal sphincter and the receptors involved were investigated on isolated preparations from rats, guinea pigs and humans. Histamine exerted a spasmogenic effect through excitation of H1-receptors. H1-receptor selective agonists in the rat but not in the guinea pig seem to act through release of prostaglandin-like substances. Apparently H2-receptors, whose stimulation causes relaxation of the sphincter, do not occur in the LES of rat and human whereas they are present in the guinea pig. H2-receptor antagonists exerted different and sometimes opposite effects and this suggests that their actions depend on the specific molecules and not on the H2-receptor blockade. The significance and the importance of the above findings are discussed.

Animals↗
PubMed1982

Cholinergic-like effects of the new histamine H2-receptor antagonist ranitidine.

The new H2-receptor blocker ranitidine, together with the effect on histamine H2-receptors, possesses a series of cholinergic-like actions: it provokes atropine-sensitive contractions of several isolated smooth muscle preparations from different animal species and it potentiates the stimulant effect of acetylcholine. Moreover it contracts human lower esophageal sphincter in vivo, an effect which is completely prevented by small doses of atropine. Finally, ranitidine potentiates the stimulant effect of bethanechol and of carbachol on salivary glands of the rat while leaving unaffected the secretagogue effect of physalaemin which is known to be completely independent of the cholinergic system. In the in vivo experiments the doses of ranitidine capable of eliciting cholinergic-like effects were of the same order of magnitude as those necessary to cause the H2-receptor blockade.

Animals↗
PubMed1982

Different effects of cimetidine and ranitidine on gastric emptying in rats and man.

Cimetidine and ranitidine were tested for their effect on gastric emptying in the rat. At low doses, cimetidine was inactive, whereas it significantly delayed emptying rate when administered at higher doses. Ranitidine always accelerated gastric emptying. At variance with rats, ranitidine delayed human gastric emptying whereas cimetidine was completely inactive. All these data are consistent with the idea that these effects of H2-antagonists are independent of H2-receptor blockade.

Animals↗
PubMed1982

Histamine H2-antagonists modify gastric emptying in the rat.

1 Histamine H2-receptor antagonists were tested for their effect on gastric emptying in the rat. 2 At low doses all the compounds were inactive except for burimamide which delayed and ranitidine which accelerated gastric emptying. 3 At high doses burimamide, metiamide, cimetidine and oxmetidine delayed, whereas ranitidine accelerated gastric emptying; tiotidine remained ineffective. 4 Changes in emptying rate were not accompanied by changes in emptying pattern which, with all the compounds examined, proceeded, as in the controls, by apparent first order kinetics. 5 The mechanism of the ranitidine-induced acceleration of gastric emptying seemed to be connected with an interference with the cholinergic system, whereas the mechanism of cimetidine- and oxmetidine-induced slowing of gastric emptying was apparently related to cholinolytic and possibly also relaxant effects of the compounds. 6 These different effects of the various H2-blockers are consistent with the idea that changes in emptying rate are independent of H2-receptor blockade.

Animals↗
PubMed1982

Inhibition of gastric emptying by bombesin in man.

Bombesin, administered by intravenous infusion (5 ng . kg-1 . min-1) for 60 min, significantly delayed gastric emptying of solids in man and strongly potentiated the gastrin response to food. However, no correlation was found between the difference in the integrated gastrin response (to meal and to meal plus bombesin) and the degree of delay in emptying. The effect of the peptide is most likely connected with the strong contraction of the gastroduodenal junction pinpointed in previous investigations.

Adult↗