Picture of two heads

Open Access research that challenges the mind...

The Strathprints institutional repository is a digital archive of University of Strathclyde research outputs. Strathprints provides access to thousands of Open Access research papers by University of Strathclyde researchers, including those from the School of Psychological Sciences & Health - but also papers by researchers based within the Faculties of Science, Engineering, Humanities & Social Sciences, and from the Strathclyde Business School.

Discover more...

Differential coupling of the human P2Y11 receptor to phospholipase C and adenylyl cyclase

Qi, Ai-Dong and Kennedy, C. and Harden, T. Kendall and Nicholas, Robert A. (2001) Differential coupling of the human P2Y11 receptor to phospholipase C and adenylyl cyclase. British Journal of Pharmacology, 132 (1). pp. 318-326. ISSN 0007-1188

Full text not available in this repository. (Request a copy from the Strathclyde author)

Abstract

1 The human P2Y(11) (hP2Y(11)) receptor was stably expressed in two cell lines, 1321N1 human astrocytoma cells (1321N1-hP2Y(11)) and Chinese hamster ovary cells (CHO-hP2Y(11)), and its coupling to phospholipase C and adenylyl cyclase was assessed. 2 In 1321N1-hP2Y(11) cells, ATP promoted inositol phosphate OF) accumulation with low muM potency (EC50 = 8.5 +/- 0.1 muM), whereas it was 15 fold less potent (130 +/- 10 muM) in evoking cyclic AMP production. 3 In CHO-hP2Y(11) cells, ATP promoted IP accumulation with slightly higher potency (EC50 = 3.6 +/- 1.3 muM) than in 1321N1-hP2Y(11) cells, but it was still 15 fold less potent in promoting cyclic AMP accumulation (EC50 = 62.4 +/- 15.6 muM) than for IP accumulation. Comparable differences in potencies for promoting the two second messenger responses were observed with other adenosine nucleotide analogues. 4 In 1321N1-hP2Y(11) and CHO-hP2Y(11) cells, down regulation of PKC by chronic treatment with phorbol ester decreased ATP-promoted cyclic AMP accumulation by 60-80% (P < 0.001) with no change in its potency. Likewise, chelation of intracellular Ca2+ decreased ATP-promoted cyclic AMP accumulation by <similar to>45% in 1321N1-hP2Y(11) cells, whereas chelation had no effect on either the efficacy or potency of ATP in CHO-hP2Y11 cells. 5 We conclude that coupling of hP2Y(11) receptors to adenylyl cyclase in these cell lines is much weaker than coupling to phospholipase C, and that activation of PKC and intracellular Ca2+ mobilization as consequences of inositol lipid hydrolysis potentiates the capacity of ATP to increase cyclic AMP accumulation in both 1321N1-hP2Y(11) and CHO-hP2Y1(1) cells.