Whether phenylephrine exerts inotropic effects through α‐ or β‐adrenoceptors depends upon the relative receptor populations

Abstract

Phenylephrine produced concentration-related positive inotropic responses in isolated left atria and papillary muscles of guinea-pigs and rats. In rat tissues, these responses were unaffected by propranolol but antagonized by prazosin and therefore mediated via alpha 1-adrenoceptors. The alpha 1-adrenoceptor agonist methoxamine also exerted positive inotropic effects in these rat tissues. The maximum alpha-adrenoceptor-mediated effect of methoxamine (relative to the isoprenaline maximum) was greater than that of phenylephrine in left atria (in the presence of propranolol), whereas in papillary muscles phenylephrine exerted the greater maximum. In guinea-pig papillary muscles, the response to phenylephrine was unaffected by prazosin but was antagonized by propranolol and therefore caused by stimulation of beta-adrenoceptors. Methoxamine had no effect in guinea-pig papillary muscles. Guinea-pig left atria produced biphasic concentration-response curves for phenylephrine, the lower portion being antagonized by phentolamine and was therefore alpha-adrenoceptor-mediated, while the upper portion was antagonized by propranolol and therefore beta-adrenoceptor-mediated. Methoxamine exerted a small inotropic response, the maximum of which was similar to that of the first component of the phenylephrine response. Phenylephrine was a partial agonist for the cardiac beta-adrenoceptor. The density of rat ventricular alpha-adrenoceptors was 4 times greater than beta-adrenoceptor density, as measured by [3H]-prazosin and [3H]-dihydroalprenolol binding. This explains why the responses of rat papillary muscles were alpha-adrenoceptor-mediated. In contrast, the density of beta-adrenoceptor binding sites in guinea-pig ventricles was 6 times greater than the alpha-adrenoceptor density. This explains why the phenylephrine responses were beta-adrenoceptor-mediated in guinea-pig papillary muscles. In the left atria of guinea-pigs, which displayed both alpha- and beta-adrenoceptor-mediated responses, the densities of alpha- and beta-adrenoceptor binding sites were similar. Thus, phenylephrine exerts positive inotropic effects through alpha- or beta-adrenoceptors depending upon their relative densities.

Modelling of α1‐adrenoceptor‐mediated temporal dynamics of inotropic response in rat heart to assess ligand binding and signal transduction parameters

“…Third, we found no significant effect of 1 µmol·L −1 propranolol on the phenylephrine‐induced increase in LVDP (data not shown). This is in accordance with the results by Chess‐Williams et al. (1990) but in disagreement with those of Silva et al.…”

Label-Free Dynamic Mass Redistribution Reveals Low-Density, Prosurvival α1B-Adrenergic Receptors in Human SW480 Colon Carcinoma Cells

“…Phenylephrine has been reported to activate b-ARs in human vascular beds (Torp et al, 2001), rabbit left ventricle (Wagner et al, 1974), and guinea pig ventricles (Chess-Williams et al, 1990), depending on the relative density of a-versus b-ARs expressed. Thus, we assayed the efficacy of AR subtype-selective antagonists to block phenylephrine-stimulated DMR responses.…”

Can the adrenergic system be implicated in the pathophysiology of bladder pain syndrome/interstitial cystitis? A clinical and experimental study

“…Also, this study does not elucidate the adrenoreceptor subtypes that may be implicated in the bladder changes induced by adrenergic stimulation. Noradrenaline might stimulate both alpha and beta adrenoreceptors, while PHE, although acting preferentially on alpha adrenoreceptors, might also induce beta‐adrenergic mediated effects . Concerning beta adrenoreceptors, human bladder express the beta3 subtype .…”