Histamine receptors and interactions between second messenger transduction systems.

Abstract

Histamine H1- and H2-receptors have been classically associated with two distinct intracellular second messenger systems. H2-receptors are coupled via a Gs regulatory protein to adenylate cyclase and stimulate cyclic AMP formation, while H1-receptors mediate many of their effects via the products of inositol phospholipid hydrolysis. It is becoming clear, however, that there is a substantial 'cross-talk' between these intracellular second messenger systems in a number of tissues. In guinea-pig cerebral cortical slices, H1-receptor stimulation can augment the direct cyclic AMP responses to adenosine or H2-receptor stimulation via a mechanism which appears to involve both products of inositol phospholipid hydrolysis, inositol triphosphate and diacylglycerol. In contrast, a reverse interaction can occur in bovine tracheal smooth muscle and agents which raise intracellular cyclic AMP levels can inhibit H1-receptor-mediated inositol phospholipid hydrolysis. In addition to these interactions between cyclic AMP and phosphoinositide signalling systems, the H1-receptor-mediated inositol phospholipid response in mammalian cerebral cortex can be regulated (both positively and negatively) via mechanisms which do not involve changes in cyclic AMP levels.