Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:4.6.1.1 (adenylate cyclase)
 19,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Prostaglandins E1 and E2 stimulate cyclic AMP accumulation in pig epidermis and in human epidermis from patients with psoriasis. Prostaglandins A1,A2 and F2alpha are relatively ineffective. The fact that this stimulation is not inhibited by a beta-blocker (propranolol) and that the stimulation by prostaglandin E2 and adrenaline is additive indicates that each drug acts independently on the epidermal adenyl cyclase system. In other words, prostaglandins E1 and E2 act on a site other than the beta-receptor of adenyl cyclase in epidermis. The stimulation by prostaglandins E1 and E2 is not additive; hence they probably act on the same site. Concentrations of prostaglandin E above 3X10(-7) M are effective in causing stimulation. This concentration may be within the physilogical range and the contribution of endogenous prostaglandin levels in the control of intracellular cyclic AMP levels cannot be disregarded.
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PMID:Prostaglandins and cyclic AMP in epidermis. Evidence for the independent action of prostaglandins and adrenaline on the adenyl cyclase system of pig and human epidermis, normal and psoriatic. 16 16

The total membrane-bound ATP hydrolytic activity in human epidermis is due to the activities of at least three differently located enzymes, namely Mg++-activated ATPase, phosphomonoesterase and adenyl cyclase. Cytochemical studies on psoriatic epidermis with various inhibitory and stimulatory substances showed reduced activities of ATPase and phosphomonoesterase, and a lack of sensitivity of adenyl cyclase to specific stimulators such as isoproterenol and glucagon. Since no differences of basal adenyl cyclase activity were observed between normal and psoriatic human skin without stimulation, it seems likely that in psoriasis a latent defect of adenyl cyclase may exist, resulting in a deficient response of this enzyme to regulatory agents. In conclusion, the present study reveals that not a single enzyme but the entire membrane-bound nucleotide metabolism is altered in psoriatic keratinocytes, causing a disturbance of the membrane-bound energy utilization, similar to findings in proliferating tumour cells.
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PMID:Ultrastructural localization and differentiation of membrane-bound ATP utilizing enzymes including adenyl cyclase in normal and psoriatic epidermis. 17 85

The system glycocalyz - membrane bound enzymes - cAMP may be regarded as a regulatory mechanism for the control of epidermal growth. The glycocalyz of the epithelial cell membrane is obviously a receptor and accumulator for agents stimulating adenyl cyclase and other membrane-bound enzymes of energy utilisation; cAMP, on the other hand, serves as an intracellular 'mediator' between proliferative stimuli and the DNA of the keratinocytes. Numerous cytological, cytochemical, and enzymatic biochemical studies indicate that this mechanism is profoundly disturbed in psoriasis, particularly at the membrane-bound stage.
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PMID:[Membrane defect as a basic disorder of the growth control mechanism in psoriasis pathogenetic concept and therapeutic consequences (author's transl)]. 17 49

Isoproterenol and sodium fluoride stimulated adenyl cyclase activity was detected in epidermal tissue from 2 patients with untreated psoriasis by an electron microscopic cytochemical technique. Adenyl cyclase activity was present on the outer surface of the cell membranes, predominantly in the basal cells and in the 4-5 lower Malpighian cell layers, while the superficial layers, stratum granulosum and stratum corneum showed no activity. The precipitates (lead-PPi complexes) after isoproterenol stimulation were larger and fewer in number than those seen after sodium fluoride stimulation. Isoproterenol stimulation was abolished by propranolol. Neither the uninvolved epidermis from the 2 patients with psoriasis nor the normal skin from 2 volunteer individuals showed any difference from the psoriatic epidermis.
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PMID:Electron microscopic cytochemical demonstration of adenyl cyclase activity in psoriatic epidermis. 86 75

Glucagon and beta-adrenergic compounds such as 1-isoproterenol stimulated the low activity of an ATP-utilizing enzyme located on the cell membranes of normal keratinocytes. Addition of beta-antagonist propranolol to the incubation medium prevented the stimulatory effect of 1-isoproterenol. We considered, therefore, the reaction product being due to epidermal membrane-bound adenyl cyclase activity. In psoriatic epidermis the basal adenyl cyclase activity was low, similar to normal epidermis, however, glucagon and 1-isoproterenol failed to stimulate the enzyme activity in psoriasis under the same conditions. It seems, therefore, that the beta-adrenergic-cAMP cascade as a regulatory epidermal control mechanism of induced proliferation is ineffective in this disease.
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PMID:[Lack of beta-adrenergic stimulation of membrane bound adenyl cyclase in psoriasis as compared to normal epidermis (author's transl)]. 124 87

1,25-dihydroxyvitamin D3 (1,25(OH)2D3) is suggested to be involved in the regulation of keratinocyte proliferation and differentiation. Recent evidence also indicates its potential value for the treatment of psoriasis, where the alteration of various transmembrane signalling systems has been well documented. Using porcine epidermis, we investigated the effect of 1,25(OH)2D3 on adenylate cyclase and protein kinase C systems, both of which are markedly altered in the psoriatic hyperproliferative epidermis. The effect was compared with that of another anti-psoriatic agent, hydrocortisone. Neither 1,25(OH)2D3 nor hydrocortisone revealed any effect on cyclic AMP levels or adenylate cyclase responses of epidermis. Long-term (24 h) hydrocortisone treatment, however, resulted in increased beta-adrenergic-, and prostaglandin E-adenylate cyclase responses. 1,25(OH)2D3-treatment had no effect on the epidermal adenylate cyclase responses following 24 h of incubation. The addition of both 1,25(OH)2D3 and hydrocortisone to the incubation medium resulted in the attenuation of the hydrocortisone-induced beta-adrenergic-, and prostaglandin E-adenylate cyclase responses of the epidermis. Neither agent had any effect on the cholera toxin-induced and forskolin-induced cyclic AMP accumulations of the epidermis. Neither 1,25(OH)2D3 nor hydrocortisone had any effect on the epidermal protein kinase C activity. It has been suggested that various anti-psoriatic agents might reveal their effect through the modulation of the adenylate cyclase system. Since 1,25(OH)2D3 had no effect when it was added singly to the incubation medium and rather inhibited hydrocortisone-induced adenylate cyclase stimulation, it is suggested that 1,25(OH)2D3 reveals its therapeutic efficacy through the mechanism, probably independently of the adenylate cyclase system.
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PMID:Effect of 1,25-dihydroxyvitamin D3 on adenylate cyclase and protein kinase C in pig epidermis. 167 19

It has been known that beta-adrenergic adenylate cyclase response is decreased in psoriatic-involved epidermis. Since the immunosuppressive agent, cyclosporin A, is reported to be effective on psoriasis clinically, the effect of cyclosporin A on beta-adrenergic adenylate cyclase response in pig skin was examined in vitro. Therapeutic serum levels of cyclosporin A (100-400 ng/ml) augmented the beta-adrenergic adenylate cyclase response of the epidermis. Highest levels of cyclosporin A (2-20 micrograms/ml) did not have any effect on its response. Both low Km and high Km cyclic AMP phosphodiesterases were not affected by cyclosporin A. Therefore, it is suggested that the clinical efficacy of cyclosporin A on psoriasis can be explained partially by its direct effect on the keratinocyte itself.
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PMID:Cyclosporin A induced augmentation of the beta-adrenergic adenylate cyclase response of pig epidermis. 284 37

The changes in cAMP, cGMP, adenylate cyclase, cyclic phosphodiesterase, and prostaglandins in psoriatic epidermal cells were compiled and critically discussed. The results of the pertinent studies permit the assumption that therapeutic approaches in psoriasis via the system of cyclic nucleotides and prostaglandins might be promising.
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PMID:Cyclic nucleotides and prostaglandins in psoriasis. 624 71

Epidermal adenylate cyclase can be activated independently by epinephrine, adenosine and histamine resulting in the accumulation of cyclic AMP. Using the uninvolved and involved keratome-sliced skin from psoriatic patients, we investigated the effects of these agents in vitro on the intra-cellular cyclic AMP levels of the skin. In the involved skin of psoriasis, epinephrine-induced cyclic AMP accumulation was decreased, whereas no decrease in adenosine- or histamine-induced cyclic AMP accumulation was seen. Since keratome-sliced skin samples had various amounts of dermal contamination, we also investigated the effect of epinephrine on the "pure" epidermal cyclic AMP level. After the incubation with epinephrine, pure epidermal samples, which were micro-dissected free from stratum corneum, dermis and skin appendages, were assayed for cyclic AMP level. Again cyclic AMP accumulation was decreased in the involved skin. Thus epinephrine-induced cyclic AMP accumulation was shown to be decreased in the involved epidermis of psoriasis.
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PMID:[Cyclic AMP accumulation in psoriatic skin: differential responses to epinephrine, AMP and histamine (author's transl)]. 627 83

Microsomal aryl hydrocarbon hydroxylase (AHH) activity was measured in suction separated epidermis from forearm skin of thirteen patients with localized palmo--plantar pustular psoriasis and thirteen normal subjects before and after induction by benzanthracene. AHH activity had a mean value of 2 . 32 micrometer 30H-BP/mg microsomal protein/h +/- 0 . 23 (s.e.) in the patients and 3 . 41 +/- 0 . 23 in the normal subjects. AHH induction was also decreased with a mean value of 1 . 15 +/- 0 . 1 (s.e.) compared with 1 . 98 +/-- 0 . 14 for the normal subjects. Since in twelve of the patients the psoriasis had always been localized to the palms and soles, the decreased basal and induced AHH activity appears to be a primary characteristic of psoriatic skin; AHH activity initiate an increase in epidermal cell turnover through modulation of prostaglandin and adenylate cyclase activity.
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PMID:Decreased epidermal aryl hydrocarbon hydroxylase and localized pustular psoriasis. 742 3


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