A(2b) receptor mediates adenosine inhibition of taurine efflux from pituicytes

Recent work suggests that part of the control of vasopressin output is mediated by taurine released from pituicytes, the astroglial cells of the neurohypophysis. Taurine release, in turn, is stimulated by hypotonic conditions and by vasopressin itself. As adenosine is generated from ATP co-released with vasopressin, it appeared important to study its effects on taurine efflux from pituicytes.

We measured radioactive efflux from cultured pituicytes and whole neurohypophyses pre-loaded with [(3)H]taurine. Cultured pituicytes were also used to study adenosine-receptor mRNA expression. Taurine efflux elicited by hypotonic shocks is approximately 30-50% smaller in the presence of 10 microM adenosine or 1 microM NECA (5'-N-ethylcarboxamidoadenosine). Both compounds also inhibited basal efflux in a manner that was not immediately reversible. Agonists of the adenosine A1-, A2a- or A3-receptor subtypes have no relevant effect on basal taurine release, and the A1-receptor antagonist DPCPX (8-cyclopentyl-1,3-dipropylxanthine) has no effect on the inhibition of release by NECA. In turn, the A2b-receptor antagonists MRS 1706 {N-(4-acetylphenyl)-2-[4-(2,3,6,7-tetrahydro-2,6-dioxo-1,3-dipropyl-1H-purin-8-yl)phenoxy]acetamide} or alloxazine partially reverse the inhibition of basal or hypotonicity-evoked efflux by NECA. Both A1- and A2b-receptor mRNAs are expressed in pituicytes, which is consistent with an A1-receptor-mediated effect on cell morphology and an A2b-receptor-mediated effect on taurine release. Forskolin and dibutyryl cAMP mimic the inhibitory effects of purinergics on basal taurine efflux, and the adenylate cyclase inhibitor DDA (2',5'-dideoxyadenosine) partially reverses the inhibition of the hypotonic response by NECA.Conclusions. Our results suggest that purinergic inhibition of taurine efflux from pituicytes operates through A2b receptors coupled to intracellular cAMP increase. They point to a possible modulation of neurohypophysial hormone output by endogenous adenosine released in either physiological or pathological situations.