title: Involvement of protein kinase C in homologous desensitization of histamine-evoked secretory responses in rat chromaffin cells.
abstract: The secretory responses in rat adrenal chromaffin cells to histamine H1 receptor stimulation desensitize during repetitive stimulation. The rate of development of this desensitization was slowed by Ro 31-8220, a protein kinase C (PKC) inhibitor. Ro 31-8220 also reversed part of the desensitization which had been induced by earlier histamine stimulation. Phorbol 12,13-dibutyrate (PDBu), an activator of protein kinase C, inhibited histamine-evoked catecholamine (CA) secretion almost completely. The inhibitory effect of PDBu on the H1-receptor-mediated secretory response was antagonized by Ro 31-8220. Histamine induced [Ca2+]i increases due to Ca2+ entry and Ca2+ release from intracellular Ca2+ stores in fura-2-loaded adrenal medullary cells. These [Ca2+]i increases were abolished in PDBu-treated cells. These results suggest that the activation of PKC following histamine H1 receptor stimulation plays a significant role in the process of homologous desensitization of histamine-evoked secretory responses in rat chromaffin cells, through modulation by PKC of H1 receptors and/or GTP-binding proteins coupled with H1 receptors.
authors.affiliation: Department of Physiology, Niigata University School of Medicine, Japan. awarashi@med.niigata-u.ac.jp
authors.forename: A
authors.initials: A
authors.lastname: Warashina
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D002273:Carcinogens / Q000494:pharmacology; D002395:Catecholamines / Q000378:metabolism; D019439:Chromaffin Cells / Q000737:chemistry / Q000187:drug effects* / Q000201:enzymology*; D005576:Colforsin / Q000494:pharmacology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D006152:Cyclic GMP / Q000031:analogs & derivatives / Q000494:pharmacology; D003594:Cytoplasmic Granules / Q000187:drug effects / Q000201:enzymology; D003888:Desensitization, Immunologic; D004791:Enzyme Inhibitors / Q000494:pharmacology; D019204:GTP-Binding Proteins / Q000378:metabolism; D006632:Histamine / Q000494:pharmacology*; D007211:Indoles / Q000494:pharmacology; D008297:Male; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D011969:Receptors, Histamine H1 / Q000378:metabolism; D013268:Stimulation, Chemical
chemical_list: D002273:Carcinogens; D002395:Catecholamines; D004791:Enzyme Inhibitors; D007211:Indoles; D011969:Receptors, Histamine H1; D005576:Colforsin; C016276:8-bromocyclic GMP; D015240:Phorbol 12,13-Dibutyrate; D006632:Histamine; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C; D019204:GTP-Binding Proteins; D006152:Cyclic GMP; D002118:Calcium; C064758:Ro 31-8220