Selective α2-adrenoceptor activation by clonidine: effects on 45Ca2 efflux and insulin secretion from isolated rat islets

A possible role for Ca²⁺ in the α-adrenoceptor-induced inhibition of glucose-stimulated insulin secretion was studied in isolated rat islets by the use of the selective α₂-adrenoceptor agonist clonidine. We found that clonidine, in contrast to the a,-adrenoceptor agonist phenylephrine, inhibited glucose-stimulated insulin secretion at dose levels below 10^-6 mol l^-1. In islets preloaded with ⁴⁶Ca²⁺ and perifused at 2 mmol l ^l Ca²⁺, clonidine (10^-6 moll^-1) reduced the glucose (13.3 mmol l^-1)-stimulated ⁴⁶Ca²⁺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 α₂-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.