Protein kinase C-dependent and -independent mechanisms regulating the parotid substance P receptor as revealed by differential effects of protein kinase C inhibitors.
Substance P-induced inositol trisphosphate (InsP3) formation was inhibited by 1 microM-4 beta-phorbol 12,13-dibutyrate (PDBu) in rat parotid acinar cells. The inhibitory effect of PDBu was reversed by the protein kinase C inhibitors H-7 or K252a. Substance P also elicits a persistent desensitization of subsequent substance P-stimulated InsP3 formation. However, this desensitization was not inhibited by H-7. In addition, H-7 had no effect on the time course of substance P-induced InsP3 formation. These results suggest that, although activation of protein kinase C by phorbol esters can inhibit the substance P receptor-linked phospholipase C pathway, this mechanism apparently plays little, if any, role in regulating this system after activation by substance P.
Sugiya
H
H
Calcium Regulation Section, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709.
Putney
J W
JW
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D000818:Animals; D002227:Carbazoles / Q000494:pharmacology; D026121:Indole Alkaloids; D015544:Inositol 1,4,5-Trisphosphate; D007295:Inositol Phosphates / Q000378:metabolism*; D007546:Isoquinolines / Q000494:pharmacology; D008297:Male; D010306:Parotid Gland / Q000378:metabolism*; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology*; D010879:Piperazines / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors*; D051381:Rats; D011919:Rats, Inbred Strains; D018040:Receptors, Neurokinin-1; D017981:Receptors, Neurotransmitter / Q000187:drug effects; D013373:Substance P / Q000494:pharmacology*; D013403:Sugar Phosphates / Q000378:metabolism*
D002227:Carbazoles; D026121:Indole Alkaloids; D007295:Inositol Phosphates; D007546:Isoquinolines; D010879:Piperazines; D018040:Receptors, Neurokinin-1; D017981:Receptors, Neurotransmitter; D013403:Sugar Phosphates; D013373:Substance P; D015240:Phorbol 12,13-Dibutyrate; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D015544:Inositol 1,4,5-Trisphosphate; C049985:staurosporine aglycone; D011493:Protein Kinase C