PT  - JOURNAL ARTICLE
AU  - Ariel R. Ase
AU  - Ramin Raouf
AU  - Danny Bélanger
AU  - Édith Hamel
AU  - Philippe Séguéla
TI  - Potentiation of P2X1 ATP-Gated Currents by 5-Hydroxytryptamine 2A Receptors Involves Diacylglycerol-Dependent Kinases and Intracellular Calcium
AID  - 10.1124/jpet.105.089045
DP  - 2005 Oct 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 144--154
VI  - 315
IP  - 1
4099  - http://jpet.aspetjournals.org/content/315/1/144.short
4100  - http://jpet.aspetjournals.org/content/315/1/144.full
SO  - J Pharmacol Exp Ther2005 Oct 01; 315
AB  - Postsynaptic P2X1 ATP-gated channels are expressed in smooth muscle cells of the vascular and genitourinary systems, where they mediate desensitizing neurogenic contractions. Using the model of the isolated rat tail artery, we show that the vasoactive mediator 5-hydroxytryptamine (5-HT), via the 5-HT2A metabotropic receptor, regulates the desensitization kinetics of P2X1 responses by increasing their rate of recovery. Reconstituting the potentiation of P2X1 ATP-gated currents by 5-HT2A receptors in the Xenopus oocyte expression system, we provide evidence that this modulation depends on the activation of novel protein kinase C isoforms and protein kinase D (also named PKCμ) downstream of phospholipase Cβ. Other major kinases like Ca2+/calmodulin kinase II, protein kinase A, mitogen-activated protein kinases, and tyrosine kinases were found not to be involved. Moreover, we report that buffering intracellular Ca2+ ions with the chelator 1,2-bis(O-aminophenoxy)ethane-N,N,N′,N′-tetraacetic acid (BAPTA) decreases the rate of recovery of P2X1 responses and increases their sensitivity to potentiation by 5-HT2A receptors or by the diacylglycerol analog phorbol ester 12-myristate 13-acetate. We conclude that intracellular Ca2+ and a subset of diacylglycerol-dependent protein kinases regulate the activity of P2X1 receptor channels by modulating their recovery from desensitization. The American Society for Pharmacology and Experimental Therapeutics