EFFECT OF AMBREIN ON SMOOTH-MUSCLE RESPONSES TO VARIOUS AGONISTS

The pharmacological effects of ambrein (isolated from ambergris) on th e contractile responses induced by some agonists in smooth muscle prep arations were investigated. Ambrein in the concentration range of 10, 50 and 250 mu g/ml decreased the spontaneous contraction of the isolat ed rabbit jejunum, rat uterus and guinea-pig vas deferens. Ambrein-ind uced antagonism to acetylcholine (Ach) in the guinea-pig ileum was abo lished when the concentration of calcium chloride in the Tyrode's solu tion was increased to 5 mM/l. Furthermore, ambrein did not antagonise nicotine-induced contractions in the isolated rabbit jejunum or seroto nin-induced contractions in the isolated guinea-pig ileum and vas defe rens or the rat uterus. However, ambrein in the concentration range of 10, 50 and 250 mu g/ml antagonised prostaglandins (PGs) E-2, D-2, F-2 alpha, and oxytocin-induced contractions in the rat uterus in vitro. Ambrein also antagonised (+/-) noradrenaline and (-) adrenaline-induce d contractions in the isolated guinea-pig vas deferens. It is conclude d that ambrein-induced non-selective dose-dependent antagonism to the effects of some agonists (Ach, adrenaline, noradrenaline, PGs and oxyt ocin) in some smooth muscles may be due to the ability of this compoun d to interfere with the mobilisation of extracellular Ca2+ required fo r muscular contractions induced by these agonists. (C) 1998 Elsevier S cience Ireland Ltd.