Wang Gang, Dayanithi Govindan, Custer Edward E, Lemos José R
Department of Physiology and Neuroscience Program, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, MA 01655, USA.
J Physiol. 2002 May 1;540(Pt 3):791-802. doi: 10.1113/jphysiol.2002.016394.
Effects of adenosine on voltage-gated Ca(2+) 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 Ba(2+) currents, with an IC(50) of 0.875 microM. Adenosine strongly inhibited, in a dose-dependent manner (IC(50) = 2.67 microM), depolarization-triggered AVP and OT release from isolated NH terminals. Adenosine and the N-type Ca(2+) channel blocker omega-conotoxin GVIA, but not other Ca(2+) channel-type antagonists, inhibited the same transient component of the Ba(2+) current. Other components such as the L-, Q- and R-type channels, however, were insensitive to adenosine. Similarly, only adenosine and omega-conotoxin GVIA were able to inhibit the same component of AVP release. A(1) receptor agonists, but not other purinoceptor-type agonists, inhibited the same transient component of the Ba(2+) current as adenosine. Furthermore, the A(1) receptor antagonist 8-cyclopentyltheophylline (CPT), but not the A(2) 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 A(1) receptor, since it was reversed by CPT. We therefore conclude that adenosine, acting via A(1) receptors, specifically blocks the terminal N-type Ca(2+) channel thus leading to inhibition of the release of both AVP and OT.
采用穿孔膜片钳记录技术和激素特异性放射免疫分析法，研究了腺苷对大鼠离体神经垂体（NH）终末电压门控性Ca(2+)通道电流以及精氨酸加压素（AVP）和催产素（OT）释放的影响。腺苷而非5'-三磷酸腺苷（ATP），能剂量依赖性且可逆地抑制全终末Ba(2+)电流的瞬态成分，其半数抑制浓度（IC(50)）为0.875微摩尔。腺苷以剂量依赖性方式（IC(50)=2.67微摩尔）强烈抑制离体NH终末去极化触发的AVP和OT释放。腺苷和N型Ca(2+)通道阻滞剂ω-芋螺毒素GVIA，但其他Ca(2+)通道类型拮抗剂则不能，抑制Ba(2+)电流的同一瞬态成分。然而，其他成分如L型、Q型和R型通道对腺苷不敏感。同样，只有腺苷和ω-芋螺毒素GVIA能够抑制AVP释放的同一成分。A(1)受体激动剂而非其他嘌呤受体类型激动剂，抑制与腺苷相同的Ba(2+)电流瞬态成分。此外，A(1)受体拮抗剂8-环戊基茶碱（CPT）而非A(2)受体拮抗剂3,7-二甲基-1-丙炔基黄嘌呤（DMPGX），能逆转腺苷对该电流成分的抑制作用。AVP和OT释放的抑制似乎也通过A(1)受体，因为它可被CPT逆转。因此，我们得出结论，腺苷通过A(1)受体发挥作用，特异性阻断终末N型Ca(2+)通道，从而导致AVP和OT释放均受抑制。
