IDENTIFICATION OF THE SMOOTH MUSCLE EXCITATORY RECEPTORS FOR ERGOT ALKALOIDS

Abstract

In cats under sodium pentobarbitone anaesthesia the first dose of ergotamine (50 μg/kg) invariably caused retraction of the nictitating membrane and a rise of arterial blood pressure. However, the responses to the dose of ergotamine were strikingly reduced when the cats were previously treated with the adrenaline antagonists phenoxybenzamine (5 mg/kg) or ergotamine (50 μg/kg). Further experiments to identify receptors for ergotamine were carried out on three different isolated smooth muscle preparations: rabbit aorta, rat uterus and dog retractor penis. Receptors for adrenaline were selectively protected by high concentrations of adrenaline throughout exposure of the preparation to a blocking concentration of ergotamine or phenoxybenzamine. Protected muscles responded to ergotamine; unprotected muscles did not. Muscles where receptors for acetylcholine, histamine or 5-hydroxytryptamine were protected by high concentrations of these drugs did not respond to ergotamine. Ergometrine, which has no blocking action on adrenaline receptors, behaved in the same way as ergotamine; muscles which were protected by adrenaline against blockade by phenoxybenzamine responded to ergometrine, but unprotected muscles did not. The stimulant actions of adrenaline, ergotamine and ergometrine were also protected against the blocking action of phenoxybenzamine by treating the muscle with a high concentration of ergometrine instead of adrenaline. It is concluded that, in smooth muscle which can be excited by adrenaline, ergotamine and ergometrine act by combining with adrenaline receptors, and that ergotamine may therefore be regarded not only as an adrenaline antagonist but also as a partial agonist since it excites the same receptors.