Selective alpha 2-adrenoceptor activation by clonidine: effects on 45Ca2+ efflux and insulin secretion from isolated rat islets.
A possible role for Ca2+ in the alpha-adrenoceptor-induced inhibition of glucose-stimulated insulin secretion was studied in isolated rat islets by the use of the selective alpha 2-adrenoceptor agonist clonidine. We found that clonidine, in contrast to the alpha 1-adrenoceptor agonist phenylephrine, inhibited glucose-stimulated insulin secretion at dose levels below 10(-6) mol l-1. In islets preloaded with 45Ca2+ and perifused at 2 mmol l-1 Ca2+, clonidine (10(-6) mol l-1) reduced the glucose (13.3 mmol l-1)-stimulated 45Ca2+ efflux during both the first and second phases of insulin secretion. Furthermore, the inhibitory effect of clonidine on glucose (13.3 mmol l-1)-stimulated insulin secretion was partially counteracted by raising the extracellular Ca2+ concentrations. Moreover, the calcium channel agonist Bay K 8644 counteracted the inhibition by clonidine on glucose-stimulated insulin secretion. Our results suggest that selective alpha 2-adrenoceptor-induced inhibition of glucose-stimulated insulin secretion is mediated, at least partially, by restraint of Ca2+-influx. This action might in turn be exerted through interference with the voltage-dependent calcium channels.
Skoglund
G
G
Department of Pharmocology, Lund University, Sweden.
Lundquist
I
I
Ahrén
B
B
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000008:administration & dosage / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D003000:Clonidine / Q000494:pharmacology*; D005947:Glucose / Q000008:administration & dosage; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects*; D008297:Male; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains
D000316:Adrenergic alpha-Agonists; D002121:Calcium Channel Blockers; D007328:Insulin; D010656:Phenylephrine; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D005947:Glucose; D003000:Clonidine; D002118:Calcium