Histamine-induced depolarization and the cyclic AMP--protein kinase A system in isolated guinea pig adipocytes.
The relationship between histamine (Hi)-induced depolarization and the cyclic AMP system in adipocytes was studied in guinea pigs, which seem to be more sensitive than rats to Hi. Hi caused a dose-dependent depolarization in guinea pig mesenterial and epididymal adipocytes with EC50 values of 1.69 x 10(-7) M and 1.19 x 10(-7) M, respectively. Guinea pig adipocytes were 280-750 times more sensitive than rat adipocytes to Hi. Isoproterenol, forskolin and 3-isobutyl-1-methylxanthine (IBMX) also caused a depolarization, and the slopes of the concentration response lines for these drugs were almost the same as that for Hi. Furthermore, pretreatment with these drugs resulted in a potentiation of Hi-induced depolarization at lower concentrations which are not effective when each drug is used alone. In addition, Hi-induced depolarization was inhibited by pretreatment with prostaglandin E1 (PGE1) and insulin dose-dependently. The content of cyclic AMP in adipocytes was increased by Hi (10(-7) M) in association with a decrease in membrane potential. KT5720, a protein kinase A inhibitor, which provides no significant effect even at a concentration of 10(-6) M, showed an antagonistic effect on Hi-induced depolarization.
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000273:Adipose Tissue / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D000527:Alprostadil / Q000494:pharmacology; D000818:Animals; D002227:Carbazoles; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism / Q000502:physiology*; D004594:Electrophysiology; D004822:Epididymis / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D006168:Guinea Pigs; D006632:Histamine / Q000494:pharmacology*; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology; D007328:Insulin / Q000494:pharmacology; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D011494:Protein Kinases / Q000502:physiology*; D011758:Pyrroles / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar
D002227:Carbazoles; D007211:Indoles; D007328:Insulin; D011758:Pyrroles; D005576:Colforsin; C057416:KT 5720; D006632:Histamine; D000242:Cyclic AMP; D011494:Protein Kinases; D011493:Protein Kinase C; D000527:Alprostadil; D007545:Isoproterenol; D015056:1-Methyl-3-isobutylxanthine