RETARDATION OF THE NEWT LIMB REGENERATION WITH SEMICARBAZIDE, AN INHIBITOR OF HISTAMINE FORMATION.

Abstract

AbstractIt is widely known that the substance histamine is a noxious agent released from cells when they are injured. At the outset these experiments were intended to show whetherhistamine, persumably released by newt limb amputation, might also promote beginning steps in regeneration. In addition, according to a new view of the physiology of histamine, its formation metabolically by the decarboxylation of histidine is an attribute of the rapid growth of many tissues. These experiments were mainly designed to interfere with histamine production and thereby disrupt the rapid growth of the limb regenerate.Semicarbazide has been used successfully in mammals to inhibit histidine decarboxylase and decrease the rate of histamine formation. In these experiments, semicarbazide was administered to stumps of amputated newt limbs by microinfusion for many hours at a time in efforts to decrease histamine formation and retard growth.When semicarbazide was infused into the limb only in preblastemal stages of regeneration, it seemed to have no effect on the course of regeneration. When it was infused directly into the early mesenchymatous blastema, however, it retarded the expansion and differentiation of the blastema. From present evidence, it appears that histamine production may not be concerned in the initiation of limb regeneration but is probably concerned in the phase of rapid blastemal enlargement, whose primary histological attribute is cellular mitosis.