The possible role of histamine-mediated cAMP formation as a link between H2-receptor stimulation and ultrastructural changes in guinea-pig oxyntic cells.

Guinea-pig oxyntic cell tubulin has been isolated and in vitro aggregation has been studied. The spontaneous assembly of isolated tubulin was significantly accelerated and increased by 1 mmol/l GTP. Histamine and forskolin increased tubulin polymerization only when detergent dispersed oxyntic cells or crude membranes were added. The forskolin response occurred very rapidly with an EC50 of approximately 30 mumol/l and did not require GTP. Histamine promoted tubulin aggregation with an EC50 of about 5 mumol/l only in the presence of GTP. Ranitidine completely inhibited the effects of histamine. From these data it is suggested that, in the oxyntic cell, histamine H2-receptor activated adenylate cyclase and the corresponding increase in cAMP play a role in eliciting characteristic ultrastructural changes by initiating formation of microtubules as a first step in the cascade of events leading to an increase in the secretory surface area.