A symmetrical 1,4-dihydropyridine with opposite actions on K(+)-induced contractions in guinea-pig ileum.

The effects of 1,4-dihydro-2,6-dimethyl-4-phenyl-pyridine-3,5-dicarboxylic acid dimethyl ester (DHMP) on Ca2(+)-evoked contractions in potassium-depolarized guinea-pig ileum longitudinal muscle were evaluated. DHMP (1-10 nM) potentiated Ca2(+)-evoked contractions; maximum enhancement was seen at 1 nM. A concentration-dependent inhibition of Ca2(+)-induced contractility was observed at higher concentrations. Racemic BAY K 8644 (1 nM - 1 microM), on the other hand, enhanced ileum responses to Ca2+ with a maximum effect at 3 nM. BAY K 8644, but not DHMP, directly elicited concentration-dependent contractions. The results provide further support for the hypothesis that dihydropyridines can act as both Ca2+ agonists and antagonists.