Comparison of the effect of calcium withdrawal from the medium and of blockade of extracellular calcium entry by isradipine on the contractile responses of the isolated rat stomach

The role of calcium in drug-induced contractions of rat gastric fundus strips was evaluated by determining the effect of two procedures on the dose-respponse curves of agonists: a) removal of calcium from the nutrient solution and b) blockade of calcium channels with the dihydrophydine isradipine. Gastric strips were obtanied from adult Wistar rats and suspended in Tyrode solution at 37-C for contraction studies. Dose-response curves for carbachol (CCh), serotonin (5-HT), KCl and BaCl2 were constructed under the two conditions descrived above. A complete blockade of contractile effects was observed for 5-HT and KCl 60 min after calcium withdrawal of after using 3 mM (45 min) of the calcium antagonist. A lower dose of antagonist or a shorter incubation in calcium-free solution caused a partial decrease of dose-response curves, added to a 30-fold shift to the right after the calcium antagonist (1mM), or a larger than 100-fold shift 3 min after calcium removal. In contrast, dose-response curves for CCh and BaCl2 were not significantly affected by either type of treatment. It is concluded that 5-HT and KCl utilize extracellular sources of calcium, whereas CCh or BaCl2 depends on a tightly-bound calcium pool in this preparation

The serotonin paradox: drug-receptor interaction in rat vas deferens.

The contractile effect of serotonin was studied in rat vas deferens, in comparison with that of noradrenaline and tyramine, after reserpine treatment, surgical denervation, and transplantation to the colon. In reserpinized animals the effect of 5HT resembled that of tyramine, since it was strikingly reduced, in spite of a small residual effect, showing that in normal preparations the effects of 5HT and tyramine are predominantly due to the release of endogenous noradrenaline. However, in denervated or transplanted vas deferens, in which the effect of tyramine is also abolished, the effect of 5HT was potentiated. It is suggested that after chronic, long lasting depletion of endogenous noradrenaline, there are alternate mechanisms that are generated to improve the contractile effect of 5HT, but not of tyramine. The nature of these mechanisms is still unknown.