Interactions between adenosine A1- and histamine H1-receptors

Abstract

• 1.

  1. 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.

• 2.

  2. Our studies have focused on the smooth muscle cell line, DDT₁MF-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.

• 3.

  3. 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 βγ subunits from G₁ proteins could be involved in augmenting responses to calcium mobilizing receptors.