title: Beta-adrenergic stimulation induces intracellular Ca++ increase in human epidermal keratinocytes.
abstract: Intracellular Ca++ ([Ca++]i) is one of the most important second messengers of extracellular signals that induce cellular responses. In epidermal keratinocytes, both extracellular and intracellular Ca++ are reported to be important to cell differentiation and proliferation. Several mechanisms that increase [Ca++]i have been elicited in various tissues; however, in epidermal keratinocytes they remain unknown. Thus, we investigated the [Ca++]i modulation in cultured human epidermal keratinocytes and the stimulation that increases the concentration. The [Ca++]i concentration of keratinocytes was increased immediately and transiently by epinephrine. Methoxamine hydrochloride and clonidine (alpha-1- and 2-adrenergic agonists) did not induce an increase in [Ca++]i. The beta-antagonist, propranolol, inhibited the [Ca++]i increase induced by epinephrine and salbutamol (a beta-2-agonist). These results reveal that the beta-adrenergic stimulation induces an immediate and transient [Ca++]i increase in human keratinocytes. Beta-adrenergic stimulation is known to induce adenylate cyclase activation, which results in cyclic AMP accumulation through stimulatory guanosine 5-triphosphate (GTP) binding proteins in the keratinocytes. Also, epinephrine is reported to inhibit cultured epidermal cell proliferation. The effect of epinephrine has been demonstrated by cyclic AMP accumulation; however, beta-adrenergic stimulation revealed a [Ca++]i increase in keratinocytes in our study. One of epinephrine's regulatory effects on epidermal cell proliferation is assumed to occur through the [Ca++]i increase as well.
authors.affiliation: Department of Dermatology, Hokkaido University School of Medicine, Sapporo, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Koizumi
authors.forename: C
authors.initials: C
authors.lastname: Yasui
authors.forename: T
authors.initials: T
authors.lastname: Fukaya
authors.forename: A
authors.initials: A
authors.lastname: Ohkawara
authors.forename: T
authors.initials: T
authors.lastname: Ueda
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000420:Albuterol / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D003000:Clonidine / Q000494:pharmacology; D004837:Epinephrine / Q000494:pharmacology*; D016257:Fura-2; D006801:Humans; D007231:Infant, Newborn; D015603:Keratinocytes / Q000187:drug effects / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D008729:Methoxamine / Q000494:pharmacology*; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000502:physiology; D013050:Spectrometry, Fluorescence
chemical_list: D000319:Adrenergic beta-Antagonists; D011943:Receptors, Adrenergic, beta; D008729:Methoxamine; D003000:Clonidine; D000420:Albuterol; D002118:Calcium; D016257:Fura-2; D004837:Epinephrine