FURTHER OBSERVATIONS ON THE RELATIONSHIP BETWEEN SEROTONIN AND THE ADRENAL1

Abstract

Additional evidence for the profound influence of 5-hydroxytryptamine (serotonin) instituting a release of reducing material from the quartered rabbit adrenal has been accumulated. A high degree of specificity of chemical structure has been demonstrated by failure of the closely related 4- and 6-hydroxy isomers to mimic the effect of serotonin. In addition, removal or replacement of the 5-hydroxyl group with a fluorine atom destroyed activity. Marked decreases in activity were also obtained upon methylation of the amine group or substitution on the [alpha]-carbon. Concomitant introduction of amphenone and serotonin resulted in complete inhibition of the serotonin influence. On the other hand the activity of serotonin was protected by the monoamine oxidase inhibitor iproniazid. Evidence derived from the use of C14-labeled serotonin, ultraviolet analysis and chromatography performed for detecting indole amines led to the conclusion that a metabolite of serotonin could not be responsible for the increased ability to reduce the blue tetrazolium reagent.