Involvement of alpha1 and beta-adrenoceptors in adrenaline stimulation of the glucagon-secreting mouse alpha-cell.
Stimulation of glucagon release and inhibition of insulin secretion from the islets of Langerhans are important for the blood-glucose-elevating effect of adrenaline. The mechanisms by which adrenaline accomplishes these actions may involve direct effects and indirect ones mediated by altered release of other islet hormones. In the present study we investigated how adrenaline affects the cytoplasmic Ca2+ concentration, which controls glucagon secretion from the pancreatic alpha-cell. The studies were performed on isolated mouse alpha-cells, which were identified by immunocytochemistry. The adrenaline effects consisted of initial mobilisation of intracellular Ca2+, accompanied by voltage-dependent influx of the ion. Part of the effect could be attributed to beta-adrenoceptor activation, as it was mimicked by the rise in cAMP and inhibited by the antagonist propranolol as well as the protein kinase A inhibitor adenosine 3',5'-cyclic monophosphorothioate Rp-isomer. alpha1-Adrenoceptors were also involved, since the antagonists phentolamine and prazosin completely abolished the effects of adrenaline. Experiments with clonidine and yohimbine gave little evidence of a role of alpha2-adrenoceptors. The results indicate that alpha1- and beta-adrenoceptors on the alpha-cells mediate adrenaline-stimulated glucagon secretion. The complete inhibition of the adrenaline response after blocking alpha1-adrenoceptors indicates an interaction with the beta-adrenergic pathway.
Vieira
Elaine
E
Department of Medical Cell Biology, Uppsala University Biomedicum, Box 571, 75123 Uppsala, Sweden.
Liu
Yi-Jia
YJ
Gylfe
Erik
E
D058646:Adrenergic alpha-1 Receptor Agonists; D058668:Adrenergic alpha-1 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D004837:Epinephrine / Q000037:antagonists & inhibitors / Q000494:pharmacology / Q000502:physiology*; D005934:Glucagon / Q000378:metabolism*; D066298:In Vitro Techniques; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D018340:Receptors, Adrenergic, alpha-1 / Q000502:physiology*; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000502:physiology*; D013997:Time Factors
D058646:Adrenergic alpha-1 Receptor Agonists; D058668:Adrenergic alpha-1 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists; D000318:Adrenergic beta-Agonists; D001786:Blood Glucose; D018340:Receptors, Adrenergic, alpha-1; D011943:Receptors, Adrenergic, beta; D005934:Glucagon; D002118:Calcium; D004837:Epinephrine