title: Protein kinase C regulation of the adenylyl cyclase system in rat prostatic epithelium.
abstract: In the context of the crosstalk between transmembrane signalling pathways, we studied the loci within the stimulatory receptor/Gs protein/adenylyl cyclase system at which protein kinase C (PKC) exerts regulatory effects in rat prostatic epithelial cells. The treatment of cells with the PKC activator phorbol 12-myristate 13-acetate (PMA) resulted in an impairment of the stimulation of adenylyl cyclase activity in terms of both potency, as seen with both vasoactive intestinal peptide (VIP) and pituitary adenylyl cyclase-activating peptide (PACAP-27), and efficacy, as seen with the beta-adrenergic agonist isoproterenol. This inhibitory effect of PMA could be prevented by cell incubation with pertussis toxin but not with cholera toxin, pointing to a Gi- but not Gs-dependent mechanism. This hypothesis was reinforced by ADP-ribosylation experiments that showed a low extent of alpha i with pertussis toxin but no change of alpha s with cholera toxin, as well as by the observation of the loss of the ability of low Gpp[NH]p doses to inhibit forskolin-stimulated adenylyl cyclase activity (a measure of Gi function) after cell treatment with PMA. However, the phorbol ester did not modify the adenylyl cyclase catalytic subunit, as shown by experiments on direct stimulation of the enzyme by forskolin. Whatever the exact mechanisms, the results support a crosstalk between the PKC and the adenylyl cyclase systems in rat prostatic epithelial cells in terms of an impairment of adenylyl cyclase stimulation, due presumably to phosphorylation of both membrane receptors (coupled to Gs) and Gi protein, but not of Gs protein or the adenylyl cyclase itself.
mesh_terms: D000244:Adenosine Diphosphate / Q000378:metabolism; D037361:Adenylate Cyclase Toxin; D000262:Adenylyl Cyclases / Q000032:analysis* / Q000378:metabolism; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D002772:Cholera Toxin / Q000494:pharmacology; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000032:analysis / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells; D004848:Epithelium / Q000201:enzymology / Q000502:physiology; D006165:Guanylyl Imidodiphosphate / Q000494:pharmacology; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009479:Neuropeptides / Q000494:pharmacology; D018377:Neurotransmitter Agents / Q000494:pharmacology; D037342:Pertussis Toxin; D010766:Phosphorylation; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D011467:Prostate / Q000166:cytology / Q000201:enzymology* / Q000502:physiology; D011493:Protein Kinase C / Q000819:agonists / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
chemical_list: C495403:Adcyap1 protein, rat; D037361:Adenylate Cyclase Toxin; D000318:Adrenergic beta-Agonists; D009479:Neuropeptides; D018377:Neurotransmitter Agents; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D010566:Virulence Factors, Bordetella; D005576:Colforsin; D006165:Guanylyl Imidodiphosphate; D014660:Vasoactive Intestinal Peptide; D000244:Adenosine Diphosphate; D002772:Cholera Toxin; D000242:Cyclic AMP; D037342:Pertussis Toxin; D011493:Protein Kinase C; D000262:Adenylyl Cyclases; D007545:Isoproterenol; D013755:Tetradecanoylphorbol Acetate