The effects of S-312-d (S-(+)-methyl-4,7-dihydro-3-isobutyl-6-methyl-4-(3- nitrophenyl)thieno[2,3-b]pyridine-5-carboxylate, CAS 120056-57-7) on the 1,4-dihydropyridine binding sites using membrane fractions prepared from monkey cerebral cortex, hippocampus, and cerebellum and on isolated monkey arteries were investigated. Specific binding of [3H]-(+)-isradipine was saturable and reversible, and of high affinity. 1,4-Dihydropyridine calcium channel antagonists competed for the binding in the order of S-312-d = nilvadipine = nicardipine > nifedipine. The effect of S-312-d on the binding was due mainly to alterations in the dissociation constant (Kd), without alterations in the binding density (Bmax). In the helical strips of cerebral, coronary, renal mesenteric, and femoral arteries contracted with K+ or prostaglandin (PG) F2 alpha, the addition of S-312-d caused a concentration-dependent relaxation. Relaxant activities of S-312-d in the cerebral arteries contracted with U-46619 (a thromboxane A2 mimetic) or endothelin-1 did not differ significantly from those in the arteries contracted with K+ or PGF2 alpha. Potencies of relaxations induced by S-312-d and 1,4-dihydropyridine calcium channel antagonists in the K(+)-depolarized mesenteric arteries correlated well with those of the binding experiment. Ca(2+)-induced contractions in the mesenteric arteries previously exposed to Ca(2+)-free medium and depolarized by excess K+ were attenuated by S-312-d, whereas PGF2 alpha-induced contractions of the arteries exposed to Ca(2+)-free medium were unaffected.(ABSTRACT TRUNCATED AT 250 WORDS)