Chloroethylclonidine is a partial alpha1A-adrenoceptor agonist in cells expressing recombinant alpha1-adrenoceptor subtypes.
Chloroethylclonidine increased cytosol [Ca2+] in rat-1 fibroblasts stably expressing alpha1a-adrenoceptors. The effect of the imidazoline was dose-dependent with a maximal effect (approximately 3-fold increase in [Ca2+]i) at 10 microM and it was blocked by phentolamine and 5-methyl urapidil, indicating that it was mediated through alpha1-adrenoceptors. Noradrenaline (1 microM) induced a much bigger effect (approximately 6-8-fold) in the same cells. When chloroethylclonidine was added before noradrenaline a dose-dependent inhibition of the effect of the natural catecholamine was observed. Chloroethylclonidine did not modified cytosol [Ca2+] in rat-1 fibroblast expressing alpha1b- or alpha1d-adrenoceptors. However, the imidazoline acutely inhibited the effect of noradrenaline in these cells. It is concluded that chloroethylclonidine interacts with alpha1a-adrenoceptors as a partial agonist inducing Ca2+ mobilization in a very short time frame and that it is able to inhibit the action of noradrenaline when co-incubated with the catecholamine in cells expressing any of the three alpha1-adrenoceptor subtypes.
Villalobos-Molina
R
R
Departamento de Farmacología y Toxicología, CINVESTAV-IPN, México, D.F., México.
Vázquez-Prado
J
J
García-Sáinz
J A
JA
D058646:Adrenergic alpha-1 Receptor Agonists; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D003000:Clonidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D051381:Rats; D018340:Receptors, Adrenergic, alpha-1 / Q000145:classification / Q000235:genetics; D011994:Recombinant Proteins / Q000145:classification / Q000235:genetics
C547715:Adra1a protein, rat; D058646:Adrenergic alpha-1 Receptor Agonists; D000316:Adrenergic alpha-Agonists; D018340:Receptors, Adrenergic, alpha-1; D011994:Recombinant Proteins; C051731:chlorethylclonidine; D003000:Clonidine; D002118:Calcium; D009638:Norepinephrine