Effect of pharmacological agents on human keratinocyte mitosis in vitro. II. Inhibition by catecholamines

Catecholamines produce mitotic inhibition in primary cell cultures of human keratinocytes probably via a block in the G2 part of the cell cycle. Epinephrine produced significant mitotic inhibition (49%) at a concentration as low as 4.5 X 10(-10) M, while its analog, isoproterenol, produced 47% inhibition at 1 X 10(-10) M. Norepinephrine elicited a 49% inhibitory response at 1 X 10(-8) M. One other catecholamine, dopamine, caused a 53% decrease in mitosis at 1 X 10(-6) M. Other structurally related amines to exhibit mitotic inhibition were phenylephrine, 58% at 1 X 10(-7) M; octopamine, 47% at 1 X 10(-5) M; and tyramine, 52% at 1 X 10(-4) M. Serotonin showed no mitotic inhibition at 1 X 10(-4) M. Various alpha and beta adrenergic blocking agents were added to the cell system. The alpha blocking agent, phentolamine, had no effect on mitosis. When added in conjunction with epinephrine or norepinephrine, no reduction of the catecholamine-induced mitotic inhibition was observed. The beta blocking agent, propranolol, by itself showed slight mitotic inhibition at 1 X 10(-6) M. When added along with epinephrine or noreinephrine, propranolol reduced the catecholamine-induced mitotic inhibition approximately 65%. In addition, propranolol blocked mitotic inhibition caused by phenylephrine, an alpha adrenergic agent. However, another beta blocking agent, dichloroisoproterenol, showed strong mitotic inhibition (53%) when added to the cultures at a concentration of 1 X 10(-8) M. The effect was reduced to zero in the presence of propranolol. These data suggest that while beta receptors may be involved in the catecholamine-induced mitotic inhibition of human keratinocytes in vitro, the nature of the receptor-molecule interaction may be complex.