Calcium antagonists and contractile responses in rat vas deferens and guinea pig ileal smooth muscle

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Abstract
The effect of extracellular Ca2+ (Ca2+ext) depletion on the loss of responsiveness of the guinea pig ileal longitudinal muscle (g.p.i.l.m.) and the rat vas deferens (r.v.d.) to K+ and cis-2-methyl-4-dimethylaminomethyl-1,3-dioxolane methiodide (CD) and K+ and noradrenaline (NA), was examined and compared with the effects of a variety of local anesthetics and Ca antagonists. Qualitative similarities are apparent with respect to the dependence of agonist-induced activity on Ca2+ext in both the g.p.i.l.m. and r.v.d. Distinct differences in the Ca2+ translocation processes in these 2 tissues, in response to the different agonists, can be shown by the use of a variety of Ca antagonists indicating that such translocation processes are both tissue and agonist selective. Contrary to the Ca2+ depletion studies, D-600 [.alpha.-isopropyl-.alpha.-[(N-methyl-N-homoveratryl)-.gamma.-aminopropyl]-3,4,5-trimethoxyphenylacetonitrile] and the usually more potent BAY-1040 [Nifedipine] showed no discrimination of action or potency in their ability to inhibit components of the NA response in the r.v.d. In contrast, D-600 and the more potent BAY-1040 selectively inhibited the tonic component of the K+ response. Treatment with SKF 525A [proadifen hydrochloride] and parethoxycaine (PC) in the g.p.i.l.m. and SKF 525A in the r.v.d. resulted in a nonselective inhibition of responses of the tissues to all stimulants. In the r.v.d. PC potentiated NA action and its methobromide (MeBr) derivative potentiated both NA and K+ action and also, like PC, partially shifted to the left the dose-response curve to Ca2+ in NA-depolarizing Ca-free Tyrode''s. The quaternary MeBr and the tertiary 2-chloroethyl (2Cl) derivatives of SKF 525A and PC were selectively more effective against CD- than K+-supported contractile activity in the g.p.i.l.m. and the 2Cl derivatives were more effective against Na than K+ responses in the r.v.d. The 2Cl derivative of PC also was more effective in antagonizing the Ca2+ dose-response curve in high-CD or high-NA than in high-K+ Ca2+-free Tyrode''s.