Colchicine-Induced Alteration of Hormone-Stimulated Cyclic AMP Synthesis in Pig Skin (Epidermis)

Abstract

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.

Adenylate Cyclase‐cyclic AMP System in Pure Epidermis Isolated by Use of Dispase

“…Previously, it was reported that hydrocortisone, colchicine, and retinoids had potentiating effects on the beta-adrenergic system of epidermis (9)(10)(11). Beta-augmentations by hydrocortisone, colchicine, and retinoids were also clearly present in the dispase-treated pure epidermal sheets, which was a remarkable contrast to results with trypsin-treated epidermis.…”

Comparative Reactivity of a Panel of Monoclonal Antibodies on Yucatan Mini‐Pig and Human Skin

“…As mini -pig skin is widely used for biochemical and pharmacological investigations (11)(12)(13)(14)(15)(16)(17)(18), Our investigations of the different reactivities of MCA allow a better understanding of crossantigenic reactivities between human and mini-pig skin. The panel of MCA used in this study confirmed the findings of previous morphological studies suggesting similarities in antigenic properties between mini -pig and human skin (1).…”

A new synthetic retinoid, E-5166, augments epidermal beta-adrenergic adenylate cyclase response

“…In a preceding report (12), we have shown that physiologic and synthetic retinoids such as all-trans-retinoic acid, Ro 10-1670 have augmentation effects on the epinephrine-induced cyclic AMP accumulation of pig skin epidermis in vitro. It was also shown that the retinoids probably work through a different mechanism from that stimuJated by glucocorti coids or colchicine, which are two known drugs with similar beta-adrenergic augmentation effects (7,8). E-5166 is a new synthetic retinoid recently developed in Japan.…”

“…The experimental procedures used were the same as those previously described (8,9). Domestic pigs weighing about 10-15 kg were intraperitoneally anaesthetized with nembutal (dose, 30 mg/kg; Abbott Laboratories, North Chicago, lll, USA).…”

“…Since these changes have been observed in experimentally-induced hyperproliferative conditions of epidermis (4,5), it has been suggested that the resultant markedJy defective beta-adrener gic response might be a concomitant feature of epidermaJ hyperproliferation (6). lnterest ingly, agents which inhibit epidermal keratinocyte prolif eration and have beneficial effects on psoriasis (such as glucocorticoids, colchicine, and protein synthesis inhibitors) have been known to augment the beta-adrenergic adenylate cyclase response of epidermis in vitro (7-9), with a possible participation of the inhibition of the phosphodiesterase activity ( 8,9).…”