TY - JOUR T1 - Modulation of N-Type Ca<sup>2+</sup> Currents by A<sub>1</sub>-Adenosine Receptor Activation in Male Rat Pelvic Ganglion Neurons JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 501 LP - 508 VL - 299 IS - 2 AU - Kyu-Sang Park AU - Seong-Woo Jeong AU - Seung-Kyu Cha AU - Boo-Soo Lee AU - In Deok Kong AU - Stephen R. Ikeda AU - Joong-Woo Lee Y1 - 2001/11/01 UR - http://jpet.aspetjournals.org/content/299/2/501.abstract N2 - Modulation of voltage-activated Ca2+ channels by adenosine was investigated in male rat major pelvic ganglion (MPG) neurons by using the whole-cell variant of the patch-clamp technique. Adenosine inhibited high voltage-activated (HVA) Ca2+ currents in a concentration-dependent manner with an EC50 of 313 nM and a maximal inhibition of 36%, respectively. Inhibition of HVA Ca2+ currents in adrenergic and cholinergic MPG neurons was similar. Adenosine did not modulate T-type Ca2+ channels present in adrenergic MPG neurons. Reverse transcription-polymerase chain reaction analysis indicated that MPG neurons express mRNAs encoding A1 and A2a receptors. Ca2+current inhibition by adenosine was mimicked byN6-cyclopentyladenosine, an A1-selective agonist (EC50 = 63 nM) and prevented by 100 nM 8-cyclopentyl-1,3-dipropylxanthine, an A1-selective antagonist. Conversely, CGS 21680, an A2a-selective agonist, displayed a relatively low potency (EC50 = 2200 nM) for inhibiting Ca2+currents. The action of adenosine was significantly attenuated by 2 mM guanosine-5′-thiodiphosphate or 500 ng/ml pertussis toxin. The voltage dependence of adenosine-induced current inhibition was evident by 1) a bell-shaped profile between the current inhibition and test potentials, 2) kinetic slowing in the presence of agonist, and 3) relief of the current inhibition by a conditioning prepulse to +80 mV. Finally, 1 μM ω-conotoxin GVIA occluded adenosine-induced current inhibition. Taken together, we concluded that adenosine inhibits N-type Ca2+ currents by activation of A1 receptors via a voltage-dependent and PTX-sensitive pathway in rat MPG neurons. Our data may explain how adenosine acts as an inhibitory modulator of ganglionic and neuromuscular transmission in the pelvic plexus. The American Society for Pharmacology and Experimental Therapeutics ER -