STUDIES ON THE MECHANISM OF SPASMOLYTIC ACTIVITY OF (O-METHYL-)-N-(2,6-DIHYDROXYBENZOYL)TYRAMINE, A CONSTITUENT OF ANIBA-RIPARIA (NEES) MEZ(LAURACEAE), IN RAT UTERUS, RABBIT AORTA AND GUINEA-PIG ALVEOLAR LEUKOCYTES

The mechanism of action of a nonspecific smooth muscle relaxant, (O-me thyl)-N-(2,6-dihydroxybenzoyl)tyramine (riparin), a constituent of Ani ba riparia (Nees) Mez. (Lauraceae) was studied in relation to Ca2+ met abolism in smooth muscle tissues and in guinea-pig alveolar leucocytes . In rat depolarized uterus, riparin inhibited in a reversible and non competitive manner CaCl2-induced contraction, a response mediated thro ugh voltage-dependent Ca2+ channels. The pD(2) value (mean +/- s.e.m.) for riparin was 4.98 +/- 0.06. When compared with sodium nitroprussid e (IC50 2.5 mu M), an antagonist of receptor-operated Ca2+ channels, r iparin was ineffective in suppressing noradrenaline-induced sustained contractions of rabbit aortic strips. However, in the aorta, the compo und inhibited intracellular calcium-dependent transient contractions o f noradrenaline and riparin (IC50 10.1 mu M) was approximately two and a half times more potent than procaine (IC50 25.5 mu M) a known inhib itor. In guinea-pig alveolar leucocytes, riparin (IC50 3.2 mu M) inhib ited intracellular Ca2+ accumulation induced by the calcium ionophore A23187. The results suggest that the inhibition of Ca2+ influx and Ca2 + release from intracellular stores contribute to the spasmolytic effe cts of riparin, which may not involve cyclic AMP generation as the lev els of this nucleotide were not increased in alveolar macrophages trea ted with riparin (10-100 mu M).