title: Alpha2-adrenoceptors inhibit antidiuretic hormone-stimulated Na+ absorption across tight epithelia (Rana esculenta).
abstract: In the present study we examined the effect of alpha-adrenergic regulation of active transepithelial Na+ absorption across the isolated frog skin epithelium. alpha-Adrenergic stimulation was achieved by addition of the adrenergic agonist noradrenaline in the presence of the beta-adrenergic blocker propranolol. alpha-Adrenergic stimulation inhibited basal as well as antidiuretic hormone (ADH)-stimulated Na+ transport. The ADH-induced increase in Na+ transport was accompanied by a membrane depolarisation due to an increase in the apical Na+ permeability. The subsequent application of noradrenaline inhibited the Na+ transport and repolarised the membrane potential, suggesting that alpha-adrenergic stimulation had reduced the apical Na+ permeability. The inhibition was abolished by the alpha2-adrenergic antagonist yohimbine whereas it was insensitive to the alpha1-adrenergic antagonist prazosin. alpha-Adrenergic stimulation had no effect on the cytosolic free [Ca2+] ([Ca2+]i). Incubation of the epithelium in the presence of ADH increased the cellular adenosine 3',5'-cyclic monophosphate (cAMP) content, an increase which was abolished by alpha-adrenergic activation. The effect of alpha-adrenergic stimulation on cAMP production was abolished by the alpha2-adrenergic antagonist yohimbine. We conclude that the noradrenaline-induced inhibition of the ADH-stimulated Na+ absorption and cAMP content is mediated by activation of alpha2-adrenoceptors. The data further indicate that the principal cells of the epithelium do not express alpha1-adrenoceptors. The noradrenaline-induced inhibition of the ADH-stimulated Na+ transport was concentration dependent, with 0.24+/-0.03 microM eliciting a half-maximal response. This alpha2-adrenergic-mediated down-regulation of Na+ absorption is achieved at a concentration of noradrenaline which begins to activate the NaCl secretion via the skin glands. The alpha2-adrenoceptors therefore appear to have considerable physiological importance.
authors.affiliation: August Krogh Institute, Copenhagen O, Denmark. CNGudme@aki.ku.dk
authors.forename: C N
authors.initials: CN
authors.lastname: Gudme
authors.forename: A L
authors.initials: AL
authors.lastname: Larsen
authors.forename: R
authors.initials: R
authors.lastname: Nielsen
mesh_terms: D058647:Adrenergic alpha-2 Receptor Agonists; D058669:Adrenergic alpha-2 Receptor Antagonists; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology; D011893:Rana esculenta; D018341:Receptors, Adrenergic, alpha-2 / Q000378:metabolism*; D011943:Receptors, Adrenergic, beta / Q000378:metabolism; D012964:Sodium / Q000378:metabolism*; D019108:Tight Junctions / Q000378:metabolism; D014667:Vasopressins / Q000494:pharmacology*; D014882:Water-Electrolyte Balance / Q000187:drug effects / Q000502:physiology*; D015016:Yohimbine / Q000494:pharmacology
chemical_list: D058647:Adrenergic alpha-2 Receptor Agonists; D058669:Adrenergic alpha-2 Receptor Antagonists; D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D018341:Receptors, Adrenergic, alpha-2; D011943:Receptors, Adrenergic, beta; D014667:Vasopressins; D015016:Yohimbine; D012964:Sodium; D000242:Cyclic AMP; D002118:Calcium; D009638:Norepinephrine; D011224:Prazosin