Interactions between adenosine A1- and histamine H1-receptors

Abstract

The interactions or "cross-talk" between adenosine A1-receptors and receptors coupled to phospholipase C (leading to the hydrolysis of inositol phospholipids) have been well documented in the literature. For example, activating the A1-receptor selectively potentiates the histamine H1-receptor stimulated hydrolysis of inositol phospholipids in guinea-pig cerebral slices. In contrast, when the adenosine receptor is activated in the cerebral cortex of mouse or man the histamine response is selectively inhibited. Our studies have focused on the smooth muscle cell line, DDT1 MF-2, derived from hamster vas deferens. These cells express A1-receptors which, in addition to the expected negative coupling to adenylate cyclase, also stimulate inositol phospholipid hydrolysis and Ca2+ mobilization. These A1-receptors also potentiate histamine H1-receptor responses, i.e. inositol phospholipid hydrolysis and Ca2+ mobilization. The mechanism(s) underlying the potentiation or inhibition of histamine H1-receptor responses by the adenosine A1-receptor remain to be unravelled. One mechanism may involve intracellular "cross-talk" at the G-protein level. This review will discuss how beta gamma subunits from G(i) proteins could be involved in augmenting responses to calcium mobilizing receptors.