Sensitivity of alpha-adrenoceptor agonists to the calcium channel activator, Bay K 8644, in canine saphenous vein

Pharmacology. 1987;35(5):272-8. doi: 10.1159/000138320.

Abstract

The purpose of the present study was to determine if the calcium channel activator, Bay K 8644, enhances the vasoconstrictor actions of selective alpha 1- and alpha 2-adrenoceptor agonists in canine saphenous vein. Phenylephrine (PE) and St 587 were used as fully and partially selective alpha 1-adrenoceptor agonists, B-HT 920 and B-HT 958 were used as fully and partially selective alpha 2-adrenoceptor agonists. Bay K 8644 (10(-8) M) markedly potentiated B-HT-958-mediated vasoconstrictor responses with a leftward shift and an increase in the maximum response of the logarithmic dose-response curve. Bay K 8644 produced less potentiation of responses to B-HT 920 and had minimal effects on responses to St 587 and PE. The intrinsic activities of the alpha-adrenoceptor agonists, as compared to the maximum response obtained by norepinephrine, in decreasing order, were PE greater than St 587 greater than B-HT 920 greater than B-HT 958, whereas the susceptibility of alpha-adrenoceptor agonists to potentiation by Bay K 8644 in decreasing order were B-HT 958 greater than B-HT 920 greater than St 587 greater than PE. These results suggest that Bay K 8644 preferentially improves the receptor-response coupling of alpha-adrenoceptor agonists with low intrinsic activity (alpha 2-agonists) versus agonists with high intrinsic activity (alpha-agonists) in canine saphenous vein.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / pharmacology*
  • Adrenergic alpha-Agonists / pharmacology*
  • Animals
  • Azepines / pharmacology
  • Clonidine / analogs & derivatives
  • Clonidine / pharmacology
  • Dogs
  • Female
  • In Vitro Techniques
  • Ion Channels / drug effects*
  • Male
  • Muscle, Smooth, Vascular / drug effects*
  • Saphenous Vein / drug effects

Substances

  • Adrenergic alpha-Agonists
  • Azepines
  • Ion Channels
  • St 587
  • 3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester
  • talipexole
  • B-HT 958
  • Clonidine