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Biomedical subjects

E Poli

Publications and source records attributed to E Poli.

At least 73 records · Page 4Linked to original sources
PubMed1985

Action of different agonists and antagonists of the cholinergic system on the rat lower esophageal sphincter.

Several compounds acting on the cholinergic system at different levels were tested for their stimulatory or inhibitory effects on the isolated lower esophageal sphincter (LES) of the rat. Results obtained with acetylcholine, bethanechol and compound McN-A343 on the one hand and atropine, pirenzepine, ganglion blocking agents and tetrodotoxin on the other, suggested that LES contraction was associated mainly with the stimulation of post-synaptic muscarinic receptors. Nicotinic receptors (both ganglionic and muscular) seem to have a minor role, if any.

Animals↗
PubMed1985

Characterization of cholinoreceptors in the rat urinary bladder by the use of agonists and antagonists of the cholinergic system.

The effects of stimulatory and inhibitory compounds acting on both nicotinic and muscarinic receptors have been evaluated in the isolated urinary bladder from adult and immature (14-18 days old) rats. Acetylcholine and bethanechol were found to induce concentration-dependent contractions which were inhibited by atropine and pirenzepine; compound McN-A-343 had a negligible contractile activity whereas DMPP had no effect at all. Responses to electrical field stimulation were abolished by tetrodotoxin (3 X 10(-8) M), enhanced by eserine (10(-8) M) and scarcely affected by hexamethonium (10(-3) M), trimethaphan (10(-3) M) and d-tubocurarine (10(-3) M). Atropine, pirenzepine and DMPP induced only a partial inhibition (50%) of the twitch response, whereas compound McN-A-343 caused a concentration-dependent inhibitory effect which was maximum (100% inhibition) at 10(-2) M. No significant differences were found between results obtained in immature and adult animals as regards either the stimulatory or the inhibitory compounds tested. It was concluded that postjunctional muscarinic receptors were responsible for the stimulatory responses observed, whereas an additional involvement of unknown mechanisms, probably not related to the cholinergic system, was suggested by the peculiar results obtained with DMPP and compound McN-A-343 on electrically-stimulated urinary bladder. Whatever the mechanisms involved, however, they are already present at the first stage of postnatal development.

(4-(m-Chlorophenylcarbamoyloxy)-2-butynyl)trimethy↗
PubMed1985

Effect of mifentidine on histamine-stimulated human atrium "in vitro": comparison with ranitidine and cimetidine.

The new H2-antagonist mifentidine was tested on human atrium, in comparison with cimetidine and ranitidine, for its activity against histamine-induced inotropic effect. Mifentidine was found to be 10 times more potent than ranitidine and 100 times more potent than cimetidine. The kinetics of the three compounds are typical of a competitive antagonism and the pA2 value was of 8.60, 6.35, 5.94 for mifentidine, ranitidine and cimetidine, respectively. Our data confirm previous findings in another isolated heart preparation, namely the guinea-pig papillary muscle.

Cimetidine↗
PubMed1984

Action of the new H2-antagonist, DA 4577, on different in vitro and in vivo preparations.

The new H2-antagonist, 4(5)-(4- isopropylaminomethyleniminophenyl )-imidazole (compound marked DA 4577), was tested for its activity on different in vitro preparations and also in the conscious cat. Its effect was compared with that of some new H2 antagonists. Two sets of experiments were performed: in the first, concerning the specific H2-receptor antagonism, DA 4577 was found to be extremely potent on the guinea-pig papillary muscle and on the human atrium stimulated by histamine (pA2 = 8.24 and 8.60 respectively). Compound DA 4577 was also found very active in inhibiting histamine-induced acid secretion from the isolated rat fundus (pA2 = 7.37) and on the dimaprit-induced gastric secretion in conscious gastric fistula cats (ID50 = 0.39 mumol kg-1 h-1). In the second set of experiments, concerning effects independent of the H2-receptor blockade (side effects of the molecule), compound DA 4577 was found to be devoid of negative inotropic effect on the human atrium in the absence of histamine stimulation; in this respect it behaved like cimetidine or ranitidine but unlike oxmetidine which showed a constant negative inotropic effect even at concentration 10 times lower than those of DA 4577. Furthermore DA 4577 was ineffective in modifying gastrointestinal motility in vitro in concentrations up to 3 X 10(-4) M, conversely from ranitidine (which stimulated motility) and oxmetidine (which inhibited motility). On the whole DA 4577 appeared to be a very potent and selective H2 antagonist which, unlike other members of the family, is devoid of non-specific effect on human atrium and on motility of the gastrointestinal tract of different animal species.

Animals↗
PubMed1984

Action of mifentidine and ranitidine on the isolated rat uterus.

The new H2-antagonist mifentidine (compound marked DA 4577) was tested for its inhibitory effect on the relaxation induced by histamine on the rat uterus and was compared with the well known H2-blocker ranitidine. Mifentidine was shown to be more effective than ranitidine (about 10 times). However whereas ranitidine behaved as a "classical" competitive antagonist, mifentidine at concentrations of 10(-7) M, caused a remarkable depression of the maximum response to histamine. This "unsurmountable" antagonism may connected with a tight binding of the compound to the receptor with a consequent low degree of dissociation. Ranitidine, but not mifentidine, at concentrations of 10(-5) M was able to potentiate the stimulatory effect of acetylcholine thus confirming also in the uterus its cholinergic-like effects so far observed mainly in the gastrointestinal tract.

Acetylcholine↗
PubMed1984

Action of oxmetidine on the rabbit aorta: comparison with some calcium entry blockers and nitroglycerin.

The novel histamine H2 receptor antagonist, oxmetidine, was tested on isolated rabbit aorta for its activity on calcium ion transport and/or utilization suggested from previous experiments. Its effect was compared with that of some "classical" calcium entry blockers (verapamil, D-600 and nifedipine) and of nitroglycerin which acts predominantly on the intracellular calcium. The effect of all these compounds was evaluated against the contraction elicited by KCl, angiotensin and noradrenaline acting by different spasmogenic mechanisms. Oxmetidine was found to antagonize to approximately the same extent the effect of the three stimulatory substances: however concentrations required for this effect were from 10 to 100 times as high as those required to inhibit histamine H2 receptors. Nitroglycerin behaved quite similarly but was approximately 10.000 times more potent than oxmetidine. Verapamil and D-600 (which were virtually identical) were always more potent (about 10 times) than oxmetidine but less efficacious on the angiotensin-induced contraction. Finally nifedipine was the most active compound on the KCl induced contraction but was almost ineffective against angiotensin. It is concluded that oxmetidine, though with a still unclear mechanism, possesses a weak but definite inhibitory effect on the availability of the intracellular calcium resembling the effect of nitroglycerin. Whether or not an action on the influx of calcium is also present cannot be surely established as long as calcium fluxes are not measured. Differences in the behaviour of the "classical" calcium entry blockers suggest that each of them possesses, together with the main well recognized effect, additional effects responsible for apparently surprising results obtained against different spasmogenic compounds.

Animals↗
PubMed1984

Failure of somatostatin to inhibit the stimulatory effect of different compounds on the lower esophageal sphincter of the rat.

In the present paper the tetradecapeptide somatostatin was investigated for its possible inhibitory effect on the lower esophageal sphincter (LES) of the rat. Somatostatin, which is known to inhibit both release of several hormones and also their actions, was found to be ineffective on the isolated rat LES. The hormone did not inhibit basal tone and did not antagonize the stimulatory effect of different peptidic and non-peptidic biological substances. The meaning and the importance of the above observations are discussed.

Animals↗
PubMed1983

Effect of some new H2-receptor antagonists on gastrointestinal motility.

Some new histamine H2-receptor antagonists were tested for their effects on gastrointestinal motility. Ranitidine was found to possess definite stimulatory effects which appeared to be connected with an interference with the cholinergic system and occurred, though in different degree, from the lower esophageal sphincter (LES) to the colon. Etintidine, on the contrary, showed a remarkable antimuscarinic effect on the LES of the rat and the guinea-pig. Cimetidine, SK&F 93479 and tiotidine were virtually ineffective whereas oxmetidine exerted a consistent inhibitory activity on both basal motility and on the contractions induced by a variety of stimulatory agents. This effect, which was completely independent of the autonomic nervous system appeared to be connected with an inhibition of the transport of calcium ions. All the above results suggest that the H2-antagonists so far available may not be absolutely selective for the H2-receptor but may be endowed with non-specific effects which could have an interest at least from a pharmacological viewpoint.

Animals↗
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

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

Stability of the diagnosis of primary affective disorder. A four-year follow-up study.

Most modern studies on depression use standardized diagnostic approaches, such as the St. Louis Criteria or the RDC. The main aim of these methods is to select reliable samples for research purposes. However, doubts have been raised as to whether the groups derived through these criteria are homogeneous. In order to investigate the stability of the diagnosis of Primary Affective Disorder (PAD), a group of 78 patients meeting the criteria for this disorder were followed for 4 years. During this period 19.2% of patients showed important psychopathological symptoms other than affective. No particular factor, apart from bipolar illness, was found to be significantly predictive of a stable diagnosis. However, the rate of diagnoses would have been greater by taking into account family history and premorbid personality of the patients. The authors conclude that other sources of information, beyond present symptoms, ought to be taken into account in order to reach more homogeneous groupings.

Adult↗
PubMed1982

[Action of a new synthetic prostaglandin on gastroesophageal motility of the rat].

A new synthetic prostaglandin, namely the 15 alpha, 16 (R), 16-methyl-16-methoxy PGE1 (compound marked MDL 646), endowed with a potent antiulcer activity, was studied for its effects on gastroesophageal motility of the rat in comparison with natural PGE1. Surprisingly enough, the two compounds were found to differ not only from a quantitative but also from a qualitative point of view. In fact, the natural PGE1 had, as expected, a relaxant effect on all the preparations examined except the rat fundus which is known to be contracted by all the different types of prostaglandins; conversely its synthetic analogue (MDL 646) showed a remarkable stimulatory effect on both "in vitro" and "in vivo" preparations. It is obvious that if these observations will be confirmed in other animal species, they could have a remarkable practical interest.

Alprostadil↗
PubMed1982

[Pharmacological effects of the combination of a spasmolytic (otilonium) with a benzodiazepine (diazepam)].

The pharmacological effects of an association represented by a myolitic agent (otilonium bromide) and a benzodiazepine (diazepam) were investigated on different in vitro preparations and on one in vivo test. In the isolated preparations both drugs administered alone showed a remarkable inhibitory effect on the motility of different areas of the digestive system both spontaneous and evoked by different stimulatory agents. Association of the two compounds gave rise to additive effects or actually to a potentiating effect according to the different tissues and animal species. Negative interference was never observed. The same was true also in the in vivo preparation ("in situ" rat pylorus). The significance and the importance of these observations are discussed also in the light of the relevant clinical implications.

Acetylcholine↗