Effect of Ca2+ modulators on acetylcholine-induced phasic and tonic contractions and A23187-induced contractions in ileal longitudinal muscle and IP3 production.

The influence of different sources of Ca2+ on the Emax and ED50 values of acetylcholine (ACh)-induced phasic and tonic contractions and on A23187-induced contractions was studied using different extracellular Ca2+ concentrations ([Ca2+]o) and the Ca2+ modulators TMB-8 and D600. IP3 production induced by both stimulants was also studied. The results are compatible with: (a) the mobilization of Ca2+ from an intracellular source as a primary event in the phasic response. (b) The primary involvement of a D600-sensitive inward Ca2+ current in the ACh-tonic response. (c) An inward D600-sensitive Ca2+ current associated with the ionophore transported ion. (d) The involvement of an IP3 independent, TMB-8 sensitive mechanism of Ca2+ mobilization involved in the A23187-induced responses.

The effect of strontium on the drug-receptor interaction on cholinergic drugs.

The effect of replacing calcium with strontium in the perfusion fluid was qualitatively and quantitatively studied in the isolated longitudinal muscle of the guinea-pig ileum. In the presence of strontium hyoscine could be considered a competitive antagonist of acetylcholine for the acetylcholine receptor of the longitudinal muscle of the guinea-pig ileum; dibenamine still blocked this receptor in an irreversible way. The equilibrium constants for acetylcholine (KA) and hyoscine (KI) were obtained in the presence of calcium (KA = 3.16 +/- 0.63 microM; KI = 0.38 +/- 0.07 nM), and strontium (KA = 7.00 +/- 0.89 microM; KI = 0.93 +/- 0.16 nM). The results show a decrease in the affinity of both drugs for the muscarinic receptor in the presence of strontium.