Histamine-Induced Depolarization and the Cyclic AMP-Protein Kinase A System in Isolated Guinea Pig Adipocytes

Abstract

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 × 10^-7 M and 1.19 × 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.