On the lack of response to catecholamine stimulation by the adenyl cyclase system in psoriatic lesions*

Abstract

When epidermis from the uninvolved skin of psoriatic patients was incubated for 5 min in Hank's medium containing adrenaline and theophylline, the cyclic AMP level consistently increased 20-30 times over the level observed when adrenaline was not added to the medium. On the other hand, when epidermis from the involved skin of psoriatic patients was incubated under the same experimental conditions, the cyclic AMP level increased only 2-5 times. Even when theophylline, and inhibitor of specific cyclic AMP-phosphodiesterase, was omitted from the medium, a clearly demonstrable difference in sensitivity to adrenaline was evident in normal appearing and lesional psoriatic epidermis. These results indicate a faulty adenyl cyclase system in the involved epidermis of psoriatic lesions rather than a defective degradation process by the specific phosphodiesterase. Since the Km for adrenaline activation of adenyl cyclase was approximately the same in both the uninvolved and the involved epidermis and since the cyclic AMP increase by adrenaline was abolished by the addition of propranolol, the basic nature of the beta-receptor (specifically the binding affinity to adrenaline) in the involved epidermis does not appear to be defective. On the other hand, the finding that the Vmax for adrenaline activation is 10-20 times higher in the uninvolved than in the involved epidermis suggests that the poor response in the involved epidermis may be due to fewer available binding sites for adrenaline in the psoriatic lesion.

Studies on the plasma membrane of normal and psoriatic keratinocytes.

“…(c) The reduced response of psoriatic keratinoeytes to adrenaline stimulation (about 30" " of normal; see Fig. ib) is consistent with figures obtained using intact epidermis (Voorhees et al, 1974;Yoshikawa et al, 1975b;lizuka et al, 1978).…”

“…Alternatively, the difference may be related to oxygen * Evidence will be presented in a subsequent communication to show that turnover of cell surface glycoprotein continues linearly during this period. tension; in epidermal slices, the higher oxygen uptake of the lesion will result in hypoxia, and hence higher cyclic AMP levels (Yoshikawa et al, 1975c), whereas in isolated keratinocytes such an effect is unlikely.…”

Maintenance of Epidermal Structures of Psoriatic Skin in Organ Culture

“…In the present paper, our modified culture method may have satisfied the necessary conditions shown in the formula of Warburg as well as the factor (F) and thus maintained the psoriatic lesion in vitro. In the present experiments, psoriatic explants maintained not only their morphological characteristics but also their biochemical characteristics, including lowered isoproterenol-stimulated cAMP levels (20) and elevated plasminogen activator activity (21)(22)(23) in the involved psoriatic epidermis.…”

Cyclic Amp Level in Different Layers of Psoriatic Epidermis

“…Also, an altered cell surface may affect a receptor for adenylate cyclase, and thereby decrease cyclic AMP levels even further. Retarded responsiveness to prostaglandin (18) E and catecholamine (19) stimulation in psoriatic epidermis has also been reported. The lower half of the epidermis could be more easily affected by dermal components which decrease responsiveness of adenylate cyclase than the upper half of the epidermis, resulting in lowered levels for cyclic AMP.…”