Effects of prolonged infusion of dopexamine on beta 1- and beta 2-adrenoceptors in guinea-pig myocardium.
1. The effects of 7-day infusion of dopexamine (50 and 200 micrograms kg-1h-1) were examined on beta 1- and beta 2-adrenoceptors in guinea-pig left ventricular membranes. 2. Receptor binding performed using the high affinity radioligand (-)-[125I]-cyanopindolol (CYP) and the beta 1-adrenoceptor antagonist CGP 20712A showed that treatment with dopexamine 200 micrograms kg-1h-1 caused a 45% reduction in beta 2-adrenoceptors and a small but not significant increase in beta 1-adrenoceptors. 3. Functional effects of dopexamine were examined in the guinea-pig isolated electrically driven left atria and K(+)-depolarized uterus. Dopexamine was an antagonist at beta 1-adrenoceptors in left atria (pKB = 4.49), and a partial agonist at beta 2-adrenoceptors in the uterus (alpha = 0.78, pD2 = 6.59). 4. The effects of dopexamine on beta 1- and beta 2-adrenoceptor density in guinea-pig ventricular myocardial membranes may be related to agonist activity at beta 2-adrenoceptors and antagonist activity at beta 1-adrenoceptors.
Williams
D W
DW
Department of Pharmacology, University of Melbourne, Parkville, Victoria, Australia.
Elnatan
J
J
Molenaar
P
P
Summers
R J
RJ
D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000818:Animals; D004298:Dopamine / Q000031:analogs & derivatives* / Q000494:pharmacology; D005260:Female; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects*; D066298:In Vitro Techniques; D015918:Infusion Pumps, Implantable; D011869:Radioligand Assay; D011943:Receptors, Adrenergic, beta / Q000187:drug effects* / Q000378:metabolism; D013997:Time Factors; D014599:Uterus / Q000187:drug effects
D000318:Adrenergic beta-Agonists; D011943:Receptors, Adrenergic, beta; C046318:dopexamine; D004298:Dopamine