The effect of 5-hydroxytryptamine and other indole derivatives on the formation of adenosine 3′,5′-cyclic monophosphate in pigeon erythrocytes

Abstract 1. 1. The effect of insulin, acetylcholine, histamine, 5-hydroxytryptamine and prostaglandins E 1 , E 2 and F 2α on basal and adrenalin-stimulated cyclic AMP content in intact pigeon erythrocytes was investigated. 2. 2. None of these compounds influenced basal cyclic AMP content, and only 5-hydroxytryptamine antagonized the effect of adrenalin. The increase in cyclic AMP with 0.55 μM adrenalin was inhibited by approx. 60% in the presence of 10 μM 5-hydroxytryptamine. The interaction between adrenalin and 5-hydroxytryptamine was competitive. 3. 3. 5-Hydroxtryptamine did not affect the rate of degradation of cyclic AMP in intact cells, but did inhibit adrenalin-stimulated cyclic AMP formation in permeable or resealed cell “ghosts”. 4. 4. The effect of 5-hydroxytryptamine to inhibit cyclic AMP accumulation was not dependent on the presence of Ca 2+ , in either intact cells or “ghosts”. 5. 5. Various indole derivatives and other compounds were tested for their ability to inhibit the effect of adrenalin on cyclic AMP accumulation. Only those derivatives with a free amino group and net positive charge in the side chain were effective. 6. 6. It was concluded that 5-hydroxytryptamine inhibits adrenalin-stimulated adenylate cyclase activity in pigeon erythrocytes, possibly by competing with adrenalin for binding to the β -adrenergic receptor.