Receptor subtypes involved in the alpha1-adrenoceptor mediated increase in 86Rb+ efflux from the rat heart

Jpn J Pharmacol. 1997 Oct;75(2):171-8. doi: 10.1254/jjp.75.171.

Abstract

The aim of this study was to determine the involvement of the different alpha1-adrenoceptor subtypes in the alpha1-adrenoceptor mediated increase in 86Rb+ efflux from rat hearts. Isolated hearts were perfused in the presence of a beta-adrenoceptor antagonist (1 microM timolol). After loading with 86Rb+, the efflux was measured during alpha1-adrenoceptor stimulation by phenylephrine (30 microM). Phenylephrine increased the 86Rb+ efflux by about 30%. Pretreatment with the preferentially alpha1B-adrenoceptor inhibitor chloroethylclonidine (CEC), reduced the response to phenylephrine by about 50%. The preferential alpha1D-adrenoceptor inhibitor BMY 7378 inhibited the response to phenylephrine by 35%, with a pKI=8.4 (95% C.I. 8.2-8.6). The response was sensitive to the preferential alpha1A-adrenoceptor inhibitors (+)niguldipine, 5-methylurapidil (5-MU) and WB-4101 at relatively high concentrations, and 5-MU inhibited the response with a pKI=7.7 (95% C.I. 7.2-8.0) in CEC pretreated hearts. In conclusion, the phenylephrine stimulated increase in 86Rb+ efflux in the rat heart is not specifically linked to only one of the alpha1-adrenoceptor subtypes, but involves the alpha1B- and the alpha1D-adrenoceptor subtypes, and probably the alpha1A-adrenoceptor subtype as well.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic alpha-Antagonists / pharmacology
  • Animals
  • Heart / drug effects
  • Heart / physiology*
  • Male
  • Phenylephrine / pharmacology
  • Rats
  • Rats, Wistar
  • Receptors, Adrenergic, alpha-1 / drug effects
  • Receptors, Adrenergic, alpha-1 / physiology*
  • Rubidium / metabolism*

Substances

  • Adrenergic alpha-Antagonists
  • Receptors, Adrenergic, alpha-1
  • Phenylephrine
  • Rubidium