Interactions between oxytocin- and calcium-modifying agents in the rat testicular capsule in vitro

We have studied the effect of drugs which affect the movement of calcium on the contractions induced by 50 and 200 nM oxytocin in the isolated testicular capsule of the rat. The ED50 for oxytocin in this preparation was 188 (+/- 66 S.E.) nM and the maximal contraction induced by oxytocin was smaller than that obtained with 10 microM of the calcium ionophore, A23187. Lanthanum (10 mM), cobalt (2 mM), EGTA (3.5 and 5 nM, 30 s exposure) and a decrease in the calcium concentration of the medium reduced the oxytocin response. The response was completely abolished after prolonged incubation with EGTA (2 mM) in a calcium-free medium. The calcium blocking agents, nifedipine and flunarizine, and the agonist, Bay K 8644, did not modify the responses to oxytocin. Verapamil, at possibly non-specific doses (10 microM), reduced the contractions while diltiazem (0.1 mM), in a prazosin (10 microM)-resistant way, and nickel (0.1 mM) increased them. Both modifiers of intracellular calcium that were used namely TMB-8 (10 microM), in a calcium-free medium, and dantrolene sodium (10 and 30 microM), with and without calcium in the medium, decreased the oxytocin response. On the whole, it seems as if both intra- and extracellular calcium were involved in the contractile effect of oxytocin, although extracellular calcium does not seem to gain access to the cell through voltage-dependent calcium channels sensitive to selective calcium entry blockers.