Search PubMed⌕ Search

Biomedical subjects

E Poli

Publications and source records attributed to E Poli.

At least 55 records · Page 3Linked to original sources
PubMed1990

Changes in the ionic environment may alter the kind of antagonism of some histamine H2-receptor blockers in the guinea pig papillary muscle.

The effect of changes in the composition of the bathing medium on the effect of histamine and histamine H2-receptor antagonists was investigated in the isolated guinea pig papillary muscle. Ringer or Krebs-Henseleit solutions were used as nutrient fluids. They mainly differed with respect to pH and to Mg2+ and H2 PO4- content. Whereas the effect of histamine was not altered by ionic changes, the antagonism by some H2 blockers was different in the two nutrient solutions. The insurmountable antagonism elicited by high concentrations (greater than or equal to 10(-6) M) of famotidine, oxmetidine and mifentidine in Ringer solution was converted to surmountable when these drugs were tested in Krebs-Henseleit solution. Conversely, the antagonism induced by ranitidine was surmountable in both solutions, and that induced by high amounts of Ioxtidine was insurmountable in both nutrient fluids. Results obtained in Ringer solution were not modified by pH adjustments or by the addition of ions present in Krebs-Henseleit medium. These results suggest that the interaction of histamine with H2 receptors in the guinea pig papillary muscle was not influenced by alterations in the ionic composition of the nutrient fluid, whereas the antagonism may be critically dependent on the ionic environment.

Animals↗
PubMed1989

Nutrient solution may alter the effect of the H2 blocker famotidine in the guinea pig papillary muscle.

The effect of different nutrient fluids (Ringer or Krebs) on the antagonism induced by the new H2 blocker famotidine against histamine was studied in the guinea pig isolated papillary muscle. The response to histamine was the same in Ringer and in Krebs solutions, as for threshold concentration and maximum response, conversely the antagonism induced by famotidine was found to be dependent on the nutrient fluid employed. It was competitive for low concentrations of the drug in both fluids, whereas the unsurmountable antagonism caused by higher concentrations in Ringer was reversed into a classical competitive one in Krebs. The potency of famotidine did not vary (pA2 values = 7.86 and 8.09 in Ringer and Krebs, respectively). The addition of PO4 or Mg++ to Ringer or the pH adjustment, in order to minimize the differences in the ionic content, did not modify the results obtained. The above data suggest that the antagonism by high concentrations of famotidine against histamine may be competitive or unsurmountable according to the nutrient fluid employed and stressed the importance of the ionic environment in the drug-receptor interaction.

Animals↗
PubMed1989

Pharmacological characterization of mare uterus motility with special reference to calcium antagonists and beta-2-adrenergic stimulants.

1. Uterine motility was studied in vitro in the myometrial tissue obtained from pregnant and non-pregnant mares. 2. The spontaneous contractions of the preparations were not modified by tetrodotoxin, by anticholinergics, antiadrenergics, histamine H1 and H2 blockers, antiserotoninergic and opioid antagonists; but disappeared in Ca2+ and Na+ free medium. 3. beta 2-adrenergic stimulants like salbutamol and hexoprenaline and the calcium channel blockers nifedipine and verapamil were effective inhibitors of the amplitude of phasic contractions (ID50S for salbutamol and nifedipine were 7.7 nM and 14.6 nM, respectively in oestrus preparations). 4. The above data indicated that the mare myometrium contractility in vitro is very sensitive to the action of beta 2 mimetic compounds and calcium antagonists; nifedipine, in particular, seems to be a very promising alternative to beta 2 stimulants in the tocolytic therapy.

Adrenergic beta-Agonists↗
PubMed1989

Inhibitory actions of amiodarone on the isolated rabbit heart and aorta.

1. The inhibitory actions of amiodarone on the isolated rabbit heart and aorta have been studied. 2. Amiodarone inhibited vasopressin- and ergonovine-induced coronary spasm, starting from a concentration of 10(-7) M which did not affect myocardial contractility to 10(-4) M, which decreased myocardial contractility. 3. Sinus node activity was largely unaffected even when the highest dose of 10(-4) M was used. 4. Amiodarone did not modify the smooth muscle contraction in rabbit aorta strips precontracted with noradrenaline or potassium. 5. Comparison with other inhibitors of the cardiovascular system (alpha- and beta-blockers, nitrates, calcium entry blockers) points out a peculiar pharmacological profile of amiodarone and indicates some doubts about its presumed anti-adrenergic properties.

Amiodarone↗
PubMed1989

Effect of calcium-channel blockers and salbutamol on the isolated mare uterus--interaction with the calcium agonist Bay K 8644.

The effects of nifedipine, verapamil and diltiazem were investigated in the isolated mare uterus in comparison with salbutamol. All the calcium-channel blockers and salbutamol inhibited the spontaneous, KC1- and electrically induced contractions; nifedipine and salbutamol were the most potent compounds. The calcium agonist Bay K 8644 (10(-8)-10(-6) mol/l) competitively antagonized the inhibitory effect of nifedipine (pA2 value = 8.54 +/- 0.06), whereas it was only slightly or totally ineffective against verapamil, diltiazem and salbutamol. These results indicate that calcium-channel blockers are potent inhibitors of mare uterine motility in vitro and emphasize the importance of Ca2+-related mechanisms in the control of uterine smooth-muscle contractility. Moreover, the validity of Bay K 8644 as a tool to distinguish classes of calcium-channel antagonists is confirmed.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1989

Action of steroid sex hormones on the isolated rabbit heart.

Steroid sex hormones, testosterone, progesterone and diethylstilbestrol, have been tested on the isolated rabbit heart. These hormones produced a negative inotropic effect (1-10 mumol/l) and an inhibitory effect on the vasopressin- or ergonovine-induced coronary spasm (0.1-10 mumol/l). Basal coronary tone was increased by testosterone and progesterone, while diethylstilbestrol induced a slight reduction of coronary perfusion pressure. The negative inotropic effect was reversed by calcium and isoprenaline, thus resembling the calcium entry blocker activity. The activation of myocardial and coronary contractility by the calcium agonist, Bay K 8644, was antagonized by all these hormones. These observations demonstrated an influence of steroid sex hormones with calcium fluxes in the isolated rabbit heart.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1989

Dihydropyridine receptors in the pregnant human uterus in vitro.

The stimulatory effect of the dihydropyridine derivative, Bay K 8644, on the isolated pregnant human uterus, and its interactions with the calcium channel blockers, nifedipine, verapamil and diltiazem and with the calmodulin inhibitor trifluoperazine were investigated. In uterine preparations showing spontaneous activity, Bay K 8644 (1 nmol/l-1 mumol/l) produced an increase in the frequency of contractions without effects on their amplitude. However, strong phasic contractions were induced in quiescent preparations. The stimulatory action of Bay K 8644 proved to be insensitive to calcium withdrawal, but was completely prevented in the presence of 1 mmol/l EGTA. Bay K 8644 shifted the inhibitory concentration-response curve of verapamil and nifedipine to the right, leaving the diltiazem- and trifluoperazine-induced effect virtually unchanged. Schild plot analysis revealed a competitive interaction of Bay K 8644 with nifedipine, while the interaction with verapamil was of the nonlinear type. These data demonstrated that the dihydropyridine derivative Bay K 8644 possesses calcium agonistic properties also in the isolated human uterus. Furthermore, the competitive interaction with nifedipine showed the existence of specific dihydropyridine receptors closely associated with the calcium channel.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1988

Pre- and postjunctional effects of histamine on the guinea pig urinary bladder: evidence for heterogeneity in the H1-receptor population?

Histamine was tested on the guinea pig isolated urinary bladder to determine both the direct effect on the muscle and the influence on the contractions induced by field stimulation. Histamine (10(-7)-10(-3) M) caused contraction of the bladder and enhancement of the atropine-resistant response to field stimulation. These effects were sensitive to the H1-receptor antagonist pyrilamine (pA2 = 8.55 and 7.07, respectively). The H2-antagonists cimetidine and famotidine were ineffective on both parameters. It is concluded that predominantly H1-receptors are present in the guinea pig urinary bladder and that they are localized both on the muscle and on non-cholinergic nerve terminals. The significant difference between the pA2 values for pyrilamine is likely to suggest a heterogeneity in the H1-receptor population.

Animals↗
PubMed1987

Effects of calcium entry blockers not connected with calcium channels inhibition.

We tested the effects of calcium entry blockers (verapamil, nifedipine, diltiazem) in comparison with nitroglycerin to investigate their inhibitory mechanisms of smooth muscle contraction not connected with the calcium blockade through calcium channels. The experiments were carried out by using isolated rabbit aorta strips in both normal and Ca2+-free solutions. Our results indicate that nitroglycerin and calcium entry blockers act on different calcium pools; the differences observed among calcium entry blockers suggest that other factors, different from calcium channels blockade (alpha-adrenergic block, unspecific effects), may be responsible for their inhibitory effect when high doses are employed.

Angiotensins↗
PubMed1987

Changes in duodenal contractility induced by "calcium antagonists" with different modes of action.

The inhibitory action of nifedipine, verapamil, diltiazem and trifluoperazine has been examined on isolated duodenum from rats and rabbits. On rabbit duodenum Ca2+ antagonists caused a reduction of the spontaneous motility in very low concentrations (10(-12)-10(-6)M). On rat duodenum Ca2+ antagonists inhibited the contractile response to BaCl2, CaCl2 and to field stimulation, nifedipine being the most potent compound (threshold concentration down to 10(-12)M). The above results indicated that Ca2+ antagonists can markedly alter the duodenal motility, both basal and drug-stimulated. The high potency of nifedipine and the selective antagonism by Bay K 8644 against nifedipine suggest the presence of a specific receptor for the dihydropyridines (DHP receptor) in the duodenum.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1986

Pharmacology of the novel H2 antagonist famotidine: in vitro studies.

The novel antiulcer drug famotidine was found to be a potent and selective inhibitor of histamine H2 receptors. Its activity on different parameters involving H2 receptors was higher than that of other compounds of the family: pA2 values were 8.33, 7.86 and 7.83 in the guinea pig atria, guinea pig papillary muscle and isolated rat gastric secretion, respectively. Apart from quantitative differences, famotidine differed from the other compounds, since it caused a competitive antagonism only at low concentrations and an unsurmountable antagonism at higher concentrations. The duration of the inhibitory action on the "in vitro" gastric secretion resembled that of cimetidine and ranitidine. Famotidine was highly effective (approximately 10 times as potent as ranitidine) also on the rat uterus (unsurmountable antagonism) and on the guinea pig gallbladder (pA2 value = 7.71). Famotidine was apparently devoid of non-specific effects concerning the gastrointestinal motility even at very high concentrations (10(-4) M). In this respect, famotidine appeared to be more selective than cimetidine and ranitidine at the H2 receptor level. The high potency, the peculiarity of the antagonism and the lack of side-effects on a number of isolated preparations, indicate this H2 antagonist as a very peculiar member of the group.

Animals↗
PubMed1986

Bay K 8644 and acetylcholine: different interaction with calcium ions in the rat duodenal muscle.

The contractile effect of the dihydropyridine analogue Bay K 8644, recently described as a Ca2+-agonist, has been evaluated in the rat isolated duodenal muscle in comparison with that of acetylcholine. Bay K 8644 (3 X 10(-10)-10(-6) mol/l) increased the duodenal motility, whereas it behaved as an inhibitor when tested at high concentrations (greater than 10(-6) mol/l). Bay K 8644 was more potent than acetylcholine (threshold concentration 3 X 10(-10) vs. 10(-8) mol/l) but less efficient. The contractile responses to Bay K 8644 and acetylcholine were reduced in calcium-free medium and abolished by addition of 1 mmol/l EGTA. In some K+-depolarized tissues, however, a contractile response to Bay K 8644 was still observed. The effects of Bay K 8644 and acetylcholine were antagonized by nifedipine and verapamil; however, a competitive antagonism was observed only for the interaction Bay K 8644-nifedipine (pA2 = 9.86). The contraction induced by Bay K 8644 was noncompetitively antagonized by low concentrations of atropine (10(-7) mol/l); Bay K 8644 (10(-7) mol/l) did not modify the response to acetylcholine, while inhibiting it at higher concentration (10(-5) mol/l); in addition, it was able to enhance the response to endogenous acetylcholine, released by field stimulation. The above results indicated that Bay K 8644 and cholinergic stimuli are strong activators of the duodenal motility in vitro. The interference of Bay K 8644 with the cholinergic system, observed in both unstimulated and electrically stimulated strips, suggested a novel site of action of this compound in the gastrointestinal muscle.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1986

Effects of 17 beta-estradiol on the isolated rabbit heart.

We have studied the effects of 17 beta-estradiol on the left ventricular pressure and on the coronary perfusion pressure in isolated rabbit heart, in order to evaluate the action of this hormone on the myocardial contractility and on the coronary resistances. 17 beta-Estradiol has induced a negative inotropic effect starting from a concentration of 10(-6) M and a vasodilation starting from 10(-7) M when administered on a vasopressin-induced coronary spasm. These effects are not related to sex or to alpha-, beta-adrenergic, histaminergic, anaesthetic-like mechanisms, but seem to interfere with calcium transport.

Animals↗
PubMed1985

The stimulatory action of the calcium channel agonist Bay K 8644 on isolated duodenal muscle. Antagonism by nifedipine and verapamil.

The action of the novel dihydropyridine analogue Bay K 8644 has been evaluated on the rat isolated duodenal muscle. Bay K 8644 (0.3 nmol/l to 1 pmol/l) increased both the tone and the phasic movements of the duodenum; the maximum response was about 60% of that to acetylcholine. Nifedipine (30 nmol/l) induced a parallel shift of the concentration-response curve to this compound to the right, without depressing the maximum response; conversely, verapamil (30 nmol/l) caused an insurmountable antagonism. Incubation of the strips in Ca2+-free medium reduced the contractile response to the calcium agonist. The spasmogenic effect of Bay K 8644 was inhibited by atropine (0.1 pmol/l) which caused a significant reduction in the maximum response to the compound. The competitive interaction between Bay K 8644 and nifedipine is consistent with an action at the same dihydropyridine binding site in the calcium channel and suggests that these compounds could be selective probes for detecting the dihydropyridine receptor also in the intestinal smooth muscle. The sensitivity of the contractile effect of Bay K 8644 to atropine may indicate an action of this compound in the cholinergic system, probably mediated by a release of acetylcholine from the nerve terminal rather than due to a direct stimulatory action at muscarinic receptors in the smooth muscle.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1985

Histamine H2 receptor antagonists may modify dog intestinal motility independently of their primary action on the H2 receptors.

Various histamine H2 receptor antagonists were tested for their possible effects on intestinal motility of the dog both "in vivo" and "in vitro". They were found to behave quite differently from one another: ranitidine exerted a small atropine-sensitive stimulatory effect by itself and strongly potentiated the stimulatory action of compounds which interfere with the cholinergic system thus confirming its cholinomimetic direct and/or indirect activities. Cimetidine and mifentidine were ineffective even at very high doses. Oxmetidine exerted an inhibitory effect independently of the kind of the stimulant agent and this suggested a direct effect on the smooth muscle. The different effects elicited by the above H2 antagonists indicate that their action on the intestinal motility is completely independent of the H2 blockade. This was furtherly confirmed by the lack of effect shown by the H2 receptor selective agonists, dimaprit and impromidine. The motor effects of ranitidine were, so far, the only ones which have been encountered, in different conditions, also in humans.

Acetylcholine↗