The possible involvement of specific dopamine receptors in the relaxing effect of dopamine in the guinea-pig isolated jejunum has been investigated. The relaxing effect of dopamine does not show the tachyphylaxis phenomenon and it is present in preparations from guinea-pigs pretreated with reserpine. These results indicate that dopamine has a direct action. Comparison of the effect of dopamine with those of other dopamine receptor agonists, i.e. apomorphine, bromocriptine and the DA1 selective fenoldopam, were made to calculate potency ratios. Since apomorphine, bromocriptine and fenoldopam were shown to relax the guinea-pig jejunum, partly behaving as indirectly acting agents, comparisons were made on reserpine-pretreated guinea-pigs. It has been found that apomorphine is 2.5 times, fenoldopam 3 times and bromocriptine 20 times more active than dopamine in relaxing the guinea-pig jejunum. The order of potency is different from that found in other dopamine receptors containing tissues. The effects of the dopamine receptor blockers, haloperidol and cis-alpha-flupenthixol and the DA1 selective blocker SCH 23390 on the relaxing effect of dopamine were also studied. The relaxing effect of dopamine was not reduced by haloperidol, cis-alpha-flupenthixol and SCH 23390. It is concluded that specific postjunctional dopamine receptors are not involved in the relaxing action of dopamine. Since dopamine is known to interact with alpha- and beta-adrenoceptors in a variety of tissues, the effects of the alpha-adrenoceptor blocker phentolamine and the beta-adrenoceptor blocker propranolol on the relaxing effect of dopamine were also studied. Noradrenaline has been used to check the responsiveness of the tissue. Phentolamine did not block the responses to dopamine and propranolol was able only to partially reduce responses to dopamine, at concentrations higher than those at which it antagonized noradrenaline. Mechanisms other than dopamine, alpha- or beta-receptor activation should be involved in the relaxing effect of dopamine in the guinea-pig jejunum.

Adrenergic alpha-Antagonists↗

PubMedDate not supplied

Effect of cromakalim on spontaneous activity of castrated rat vas deferens.

After castration rat vasa deferentia exhibited spontaneous activity. Cromakalim which acts by opening K+ channels has been shown to suppress this spontaneous activity following castration. Glibenclamide, a potent blocker of the ATP-sensitive K+ channels, inhibited this contrasting effect of cromakalim. The concentrations of cromakalim and glibenclamide that were employed are consistent with those active in different kinds of smooth muscle. The presented data are compatible with the hypothesis that castration decreases potassium conductance and that such an effect could be responsible for spontaneous activity.

Animals↗

PubMedDate not supplied

Study of the negative inotropic action of somatostatin.

Somatostatin was evaluated as a chronotropic and inotropic agent in isolated, spontaneously beating guinea-pig atria. Somatostatin (3 x 10(-5)-1 x 10(-3) mM) caused a concentration-dependent negative inotropic effect and a small reduction of atrial rate. The negative inotropic effect of somatostatin was evaluated at different concentrations of extracellular calcium, on the positive inotropic response induced by calcium and on the positive chronotropic response induced by adrenaline. Small, nonsignificant changes in atria response to somatostatin were found both with the lowest (1.25 mM) and with the highest (5 mM) calcium concentration in the medium. Somatostatin (1 x 10(-4)-1 x 10(-3) mm) did not substantially modify the positive inotropic action of calcium; this substance (1 x 10(-3 mM) caused a parallel shift to the right of the adrenaline concentration-response curve. These results suggest that the negative inotropic and chronotropic actions of somatostatin do not appear to be due to an action on the voltage-sensitive calcium channels, but rather to an action on the calcium channels excited by the stimulation of beta-receptors, whose function is probably cooperative with that of the voltage-sensitive channels.

Animals↗