EPIDERMAL ADENYLATE-CYCLASE - STIMULATION OF HISTAMINE (H-2) RECEPTOR BY TOLAZOLINE

[摘要] Tolazoline (2-benzyl-2-imidazoline) activated adenylate cyclase in pig epidermal slices resulting in the accumulation of cyclic[c]AMP. This effect was highly potentiated by the addition of the cAMP-phosphodiesterase inhibitor, theophylline. Specific histamine (H2) receptor inhibitors (metiamide and cimetidine) completely blocked the tolazoline activation of adenylate cyclase. At low concentrations (10-100 .mu.M), a histamine (H1) receptor inhibitor (diphenhydramine) and a .beta.-adrenergic blocker (propranolol) did not inhibit this effect. The stimulation of cAMP formation by the combination of tolazoline and histamine was about the same as the stimulation by histamine alone (nonadditive), whereas the stimulatory effects by tolazoline and epinephrine were additive. Tolazoline, an .alpha.-adrenergic blocker, also activates adenylate cyclase at the histamine (H2) receptor site which is distinct from the .beta.-adrenergic receptor site. Another .alpha.-adrenergic blocker, phentolamine, did not have this effect.