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...

Mechanisms of phospholipase C activation by the vasoactive intestinal polypeptide/pituitary adenylate cyclase activating polypeptide type 2 receptor

MacKenzie, C. and Lutz, E. and Johnson, M.S. and Robertson, D.N. and Holland, P.J. and Mitchell, R. (2001) Mechanisms of phospholipase C activation by the vasoactive intestinal polypeptide/pituitary adenylate cyclase activating polypeptide type 2 receptor. Endocrinology, 142 (3). pp. 1209-1217. ISSN 0013-7227

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

Abstract

The vasoactive intestinal polypeptide/pituitary adenylate cyclase-activating polypeptide type 2 (VPAC2) receptor was shown to induce both [3H]inositol phosphate ([3H]InsP)and cAMP production in transfected COS7 cells and in GH3 cells where it is natively expressed. Neither cholera toxin nor forskolin could elicit an equivalent [3H]InsP response, suggesting independent coupling of the two pathways. The VPAC2 receptor-mediated [3H]InsP response was partially inhibited by pertussis toxin (Ptx) and by the G{beta}{gamma}-sequestering C-terminal fragment of GRK2 (GRK2-ct) in COS7 and GH3 cells, whereas responses of control receptors were unaffected. Blockers of receptor-activated Ca2+ influx pathways (Co2+ and SKF 96365) also partially inhibited VPAC2 receptor-mediated [3H]InsP responses. This inhibition was not present in the component of the response remaining after Ptx treatment. A range of blockers of voltage-sensitive Ca2+ channels were ineffective, consistent with the reported lack of these channels in COS7 cells. The data suggest that the VPAC2 receptor may couple to phospholipase C through both Ptx-insensitive and Ptx-sensitive G proteins (Gq/11 and Gi/o, respectively) to generate [3H]InsP. In addition to G{beta}{gamma}, Gi/o activation appears to require receptor-activated Ca2+ entry. This is consistent with the possibility that not only G{alpha}q/11-responsive and G{beta}{gamma}-responsive isoforms of phospholipase C but also Ca2+-responsive forms may contribute to the overall [3H]InsP response.