title: Desensitization of the epidermal adenylate cyclase system: agonists and phorbol esters desensitize by independent mechanisms.
abstract: Exposure of pig epidermis to adenylate cyclase stimulators results in receptor-specific desensitization. We investigated the nature of the agonist-induced desensitization, which was compared with the phorbol ester-induced, receptor-nonspecific desensitization. Both phorbol ester-induced desensitization and the agonist-induced desensitization were accompanied by an increase in forskolin- and cholera toxin-induced cyclic AMP accumulations. The magnitude of the increase in the agonist-induced desensitization was parallel to the degree of the initial cyclic AMP accumulation; histamine and adenosine, which increase more cyclic AMP than epinephrine, resulted in a more marked increase in forskolin- and cholera toxin-induced cyclic AMP accumulations. Similarly, epidermis desensitized to multiple receptors revealed more marked forskolin- and cholera toxin-induced cyclic AMP accumulations than epidermis desensitized to a single receptor. In contrast to the phorbol ester-induced desensitization, agonist-induced desensitization was not affected by the protein kinase C inhibitors H-7 and staurosporin. Further, agonist-induced desensitization was still inducible in phorbol ester-desensitized epidermis and vice versa. In contrast to the agonist-induced desensitization, which is accompanied by the preceding adenylate cyclase stimulation, no evidence for the stimulation of the adenylate cyclase during phorbol ester treatment was obtained. Neither agonist-induced desensitization nor phorbol ester-induced desensitization affected the content of inhibitory guanine nucleotide binding protein of the epidermis, which was monitored by the pertussis toxin (IAP)-catalyzed ADP ribosylation reaction. Our results indicate that agonist-induced desensitization and the phorbol ester-induced desensitization are independent of each other. Although both processes are characterized by increased forskolin- and toxin-induced cyclic AMP accumulations, the former is accompanied by initial cyclic AMP accumulation; the latter is not.
authors.affiliation: Department of Dermatology, Asahikawa Medical College, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Iizuka
authors.forename: K
authors.initials: K
authors.lastname: Asano
authors.forename: F
authors.initials: F
authors.lastname: Ito
authors.forename: T
authors.initials: T
authors.lastname: Tamura
authors.forename: H
authors.initials: H
authors.lastname: Takahashi
authors.forename: M
authors.initials: M
authors.lastname: Tsutsui
mesh_terms: D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D000241:Adenosine / Q000494:pharmacology*; D000255:Adenosine Triphosphate / Q000494:pharmacology; D037361:Adenylate Cyclase Toxin; D000262:Adenylyl Cyclases / Q000378:metabolism*; D000470:Alkaloids / Q000494:pharmacology; D000818:Animals; D002772:Cholera Toxin / Q000494:pharmacology; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D004817:Epidermis / Q000201:enzymology*; D004837:Epinephrine / Q000494:pharmacology*; D006632:Histamine / Q000494:pharmacology*; D007546:Isoquinolines / Q000494:pharmacology; D037342:Pertussis Toxin; D010879:Piperazines / Q000494:pharmacology; D011943:Receptors, Adrenergic, beta / Q000187:drug effects; D011968:Receptors, Histamine / Q000187:drug effects; D012867:Skin; D019311:Staurosporine; D013552:Swine; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
chemical_list: D037361:Adenylate Cyclase Toxin; D000470:Alkaloids; D007546:Isoquinolines; D010879:Piperazines; D011943:Receptors, Adrenergic, beta; D011968:Receptors, Histamine; D010566:Virulence Factors, Bordetella; D005576:Colforsin; D006632:Histamine; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D000255:Adenosine Triphosphate; D002772:Cholera Toxin; D000242:Cyclic AMP; D037342:Pertussis Toxin; D000262:Adenylyl Cyclases; D019311:Staurosporine; D000241:Adenosine; D013755:Tetradecanoylphorbol Acetate; D004837:Epinephrine