Involvement of protein kinase C in homologous desensitization of histamine-evoked secretory responses in rat chromaffin cells.
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.
Warashina
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Department of Physiology, Niigata University School of Medicine, Japan. awarashi@med.niigata-u.ac.jp
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
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