Calcium-based evaluation of dose-response curves of papaverine-like relaxants in guinea-pig taenia coli.

Using CaCl2 dose-contraction curves in 165.6 mM K(+)- depolarized guinea-pig taenia coli, the maximal contraction level induced by 30 mM CaCl2, and the maximal relaxation level induced by Ca-free solution were treated and 0% and 100% relaxation, respectively. Then four kinds of contraction level were compared: (1) the normal level, (2) 5.5 microns acetylcholine (ACh)-induced contraction, and (3) 1.65 mM ACh- or 3 mM BaCl2-induced contraction in normal solution; and (4) 2.2 and 30 mM CaCl2-induced contraction in K(+) depolarizing solution. The relaxing effects of papaverine, MnCl2, and isoproterenol at these different contraction levels were compared. Papaverine- and MnCl2-induced relaxation of the higher contraction levels [a part of (2), (3) and (4)] seem to reflect a mechanism of the intracellular calcium mobilization, being quite different from relaxation induced by papaverine-like relaxants and isoproterenol at the lower contraction levels [(1) and part of (2)]. The latter phenomenon seems to reflect mechanisms related to cyclic AMP. Papaverine inhibited competitively BaCl2-induced contraction only in K(+) depolarized tissues, suggesting a mechanism of direct reaction with the intracellular Ca store.