Colchicine-induced alteration of hormone-stimulated cyclic AMP synthesis in pig skin (epidermis).

Effects of colchicine on the epidermal adenylate cyclase systems were investigated. When pig skin (epidermis) was incubated in RPMI 1640 medium without the addition of serum, the beta-adrenergic adenylate cyclase response (epinephrine-induced cyclic AMP accumulations) gradually decreased, whereas adenosine and histamine responses remained high or increased during the long-term (up to 48 h) incubation period. The addition of colchicine (1 mumol/liter) in the incubation medium resulted in an increase in the beta-adrenergic responsiveness and a decrease in adenosine and histamine responsivenesses. The effects of colchicine were both time- and concentration-dependent; they could be observed after 9-12 h incubation, and the maximal effect was obtained at a concentration of 0.1 mumol/liter. Similar effects were observed by the addition of another microtubule-disruptive agent, vinblastine. On the other hand, cytochalasin B, which affects the microfilament system, apparently decreased the beta-adrenergic response and increased adenosine and histamine responses during the long-term incubation period. The addition of serum in the incubation medium resulted in essentially the same effect as that of colchicine; in the presence of serum, colchicine-treated skin responded much more markedly to epinephrine (and much less to adenosine and histamine) than the control skin after 24- and 48-h incubation. Previously we reported that hydrocortisone has similar potentiating effects on the beta-adrenergic system of epidermis. The comparison of the effects of both compounds revealed that colchicine had a stronger effect than hydrocortisone, and furthermore, the simultaneous addition of both compounds (colchicine and hydrocortisone) in the incubation medium resulted in the more marked increase of beta-adrenergic response than the single addition of each chemical. Our overall results, coupled with the finding that hydrocortisone has no toxic effects on the adenosine- or histamine-adenylate cyclase system of epidermis, suggest that colchicine affects epidermal adenylate cyclase systems probably through a mechanism that is independent of glucocorticoid (hydrocortisone) effect.