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 leucocytes.
The mechanism of action of a nonspecific smooth muscle relaxant, (O-methyl-)-N-(2,6-dihydroxybenzoyl)tyramine (riparin), a constituent of Aniba riparia (Nees) Mez. (Lauraceae) was studied in relation to Ca2+ metabolism in smooth muscle tissues and in guinea-pig alveolar leucocytes. In rat depolarized uterus, riparin inhibited in a reversible and noncompetitive manner CaCl2-induced contraction, a response mediated through voltage-dependent Ca2+ channels. The pD2 value (mean +/- s.e.m.) for riparin was 4.98 +/- 0.06. When compared with sodium nitroprusside (IC50 2.5 microM), an antagonist of receptor-operated Ca2+ channels, riparin was ineffective in suppressing noradrenaline-induced sustained contractions of rabbit aortic strips. However, in the aorta, the compound inhibited intracellular calcium-dependent transient contractions of noradrenaline and riparin (IC50 10.1 microM) was approximately two and a half times more potent than procaine (IC50 25.5 microM) a known inhibitor. In guinea-pig alveolar leucocytes, riparin (IC50 3.2 microM) inhibited intracellular Ca2+ accumulation induced by the calcium ionophore A23187. The results suggest that the inhibition of Ca2+ influx and of Ca2+ release from intracellular stores contribute to the spasmolytic effects of riparin, which may not involve cyclic AMP generation as the levels of this nucleotide were not increased in alveolar macrophages treated with riparin (10-100 microM).
Thomas
G
G
Laboratório de Tecnologia Farmacêutica, Universidade Federal da Paraíba, João Pessoa, Brazil.
Branco
U J
UJ
Barbosa Filho
J M
JM
Bachelet
M
M
Vargaftig
B B
BB
D000818:Animals; D001011:Aorta / Q000187:drug effects*; D001549:Benzamides / Q000494:pharmacology*; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000187:drug effects; D000242:Cyclic AMP / Q000378:metabolism; D005260:Female; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007958:Leukocyte Count / Q000187:drug effects*; D008264:Macrophages / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects; D009638:Norepinephrine / Q000494:pharmacology; D010936:Plant Extracts / Q000494:pharmacology; D011817:Rabbits; D051381:Rats; D014439:Tyramine / Q000031:analogs & derivatives* / Q000494:pharmacology; D014599:Uterus / Q000187:drug effects*
D001549:Benzamides; D015220:Calcium Channels; D010936:Plant Extracts; C087987:riparin III; D000001:Calcimycin; D000242:Cyclic AMP; D002118:Calcium; D009638:Norepinephrine; D014439:Tyramine