Effect of alpha1-adrenergic stimulation of Cl- secretion and signal transduction in exocrine glands (Rana esculenta).
In the present work, the effect of stimulation of alpha-adrenergic receptors on Cl- secretion via exocrine frog skin glands was investigated. The alpha-adrenergic stimulation was performed by addition of the adrenergic agonist noradrenaline in the presence of the beta-adrenergic antagonist propranolol. In the presence of propranolol, noradrenaline had no effect on the cellular cAMP content. The Cl- secretion was measured as the amiloride-insensitive short circuit current (ISC). Addition of noradrenaline induced a biphasic increase in the ISC. The increase in ISC coincided with an increase in the net 36Cl- secretion. The noradrenaline-induced increase in ISC was dose-dependent with an EC50 of 13 +/- 0.3 microM. Epifluorescence microscopic measurements of isolated, fura-2-loaded frog skin gland acini were used to characterize the intracellular calcium ([Ca2+]i) response. Application of noradrenaline induced a biphasic [Ca2+]i response, which was dose-dependent with an EC50 of 11 +/- 6 microM. The Ca2+ plateau unlike the peak-response was sensitive to removal of Ca2+ from the extracellular medium. The noradrenaline-induced increase in the Cl- secretion as well as in [Ca2+]i was sensitive to the alpha1-adrenergic antagonist prazosine. Ryanodine and caffeine had no effect on [Ca2+]i indicating that the release was independent of ryanodine-sensitive Ca2+ stores. Noradrenaline mediated a significant increase in the cellular inositol 1,4,5-trisphosphate (IP3) content suggesting that the signal transduction pathway leading to the noradrenaline-induced increase in Ca2+ involved IP3 and a release of Ca2+ from IP3-sensitive stores.
Gudme
C N
CN
Department of Biochemistry, August Krogh Institute, University of Copenhagen, Denmark.
Nielsen
M S
MS
Nielsen
R
R
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D001692:Biological Transport / Q000187:drug effects / Q000502:physiology; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002712:Chlorides / Q000378:metabolism*; D000242:Cyclic AMP / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D005088:Exocrine Glands / Q000502:physiology*; D005260:Female; D005456:Fluorescent Dyes; D016257:Fura-2; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D011893:Rana esculenta; D018340:Receptors, Adrenergic, alpha-1 / Q000502:physiology*; D012433:Ryanodine / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D012879:Skin Physiological Phenomena / Q000187:drug effects
D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D000319:Adrenergic beta-Antagonists; D002712:Chlorides; D005456:Fluorescent Dyes; D010726:Phosphodiesterase Inhibitors; D018340:Receptors, Adrenergic, alpha-1; D012433:Ryanodine; D002110:Caffeine; D015544:Inositol 1,4,5-Trisphosphate; D011433:Propranolol; D000242:Cyclic AMP; D002118:Calcium; D016257:Fura-2; D009638:Norepinephrine; D011224:Prazosin