Adenosine inhibition via A1 receptor of N-type Ca2+ current and peptide release from isolated neurohypophysial terminals of the rat

Abstract

Effects of adenosine on voltage-gated Ca2+ channel currents and on arginine vasopressin (AVP) and oxytocin (OT) release from isolated neurohypophysial (NH) terminals of the rat were investigated using perforated-patch clamp recordings and hormone-specific radioimmunoassays. Adenosine, but not adenosine 5′-triphosphate (ATP), dose-dependently and reversibly inhibited the transient component of the whole-terminal Ba2+ currents, with an IC50 of 0.875 μm. Adenosine strongly inhibited, in a dose-dependent manner (IC50 = 2.67 μm), depolarization-triggered AVP and OT release from isolated NH terminals. Adenosine and the N-type Ca2+ channel blocker ω-conotoxin GVIA, but not other Ca2+ channel-type antagonists, inhibited the same transient component of the Ba2+ current. Other components such as the L-, Q- and R-type channels, however, were insensitive to adenosine. Similarly, only adenosine and ω-conotoxin GVIA were able to inhibit the same component of AVP release. A, receptor agonists, but not other purinoceptor-type agonists, inhibited the same transient component of the Ba2+ current as adenosine. Furthermore, the A1 receptor antagonist 8-cyclopentyltheophylline (CPT), but not the A2 receptor antagonist 3, 7-dimethyl-1-propargylxanthine (DMPGX), reversed inhibition of this current component by adenosine. The inhibition of AVP and OT release also appeared to be via the A1 receptor, since it was reversed by CPT. We therefore conclude that adenosine, acting via A1 receptors, specifically blocks the terminal N-type Ca2+ channel thus leading to inhibition of the release of both AVP and OT.