Selectivity of prenalterol for adrenergic receptor subtypes: a potential mechanism of inotropic selectivity.
To address the hypothesis that myocardial adrenergic receptors mediating chronotropy may be distinguishable from receptors mediating inotropy on the basis of existing subtype classifications, the binding properties of the inotropically selective adrenergic agonist prenalterol to receptor populations of known subtype were characterized. In competitive binding assays, prenalterol exhibited higher affinity for beta 1- than for beta 2-receptors, and a low affinity for both alpha 1- and alpha 2-receptors, in comparison with non-subtype-selective agonists. In addition, log molar displacement curves for prenalterol binding to beta 1-receptors, but not to beta 2- or alpha 2-receptors, were steepened and shifted rightward by guanine nucleotide, suggesting that prenalterol is a beta 1-agonist, but may have antagonist properties at beta 2- and alpha 2-receptors. This receptor subtype profile is similar to that of dobutamine, another inotropically selective adrenergic agonist. This concordance lends further support to the hypothesis that chronotropic responses to exogenous adrenergic agonists may be mediated selectively through beta 2-receptors.
D000318:Adrenergic beta-Agonists / Q000378:metabolism*; D000818:Animals; D004285:Dogs; D066298:In Vitro Techniques; D009200:Myocardial Contraction / Q000187:drug effects*; D009206:Myocardium / Q000378:metabolism*; D011217:Practolol / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D011294:Prenalterol; D051381:Rats; D011941:Receptors, Adrenergic / Q000187:drug effects / Q000378:metabolism*
D000318:Adrenergic beta-Agonists; D011941:Receptors, Adrenergic; D011294:Prenalterol; D011217:Practolol