Vasoconstrictor effect of the Ca2+ agonist Bay K 8644 on human cerebral arteries

Brain Res. 1989 Jun 19;490(1):133-40. doi: 10.1016/0006-8993(89)90438-1.

Abstract

The effects of Bay K 8644 on the reactivity and 45Ca2+ uptake in segments from human cerebral arteries were studied. Bay K 8644 induced concentration-dependent contractions up to 10(-6) M; 10(-5) M produced a reduction of the maximal response. The Ca2+ agonist elicited these contractions by itself, and no previous depolarization was needed. The response to Bay K 8644 was antagonized competitively by nifedipine (5 x 10(-8) and 10(-7) M, pA2 value of 8.17) and non-competitively by verapamil (10(-6), 5 x 10(-6) and 10(-5) M). The contraction induced by 10(-7) M Bay K 8644 was inhibited by a Ca2+-free medium containing 1 mM EGTA. The subsequent cumulative Ca2+ addition, caused concentration-dependent contractions up to 2.5 mM Ca2+, which were reduced by nifedipine (10(-8) and 10(-7) M) or verapamil (5 x 10(-6) and 10(-5) M). When the EGTA concentration in the Ca2+-free solution was reduced to 0.1 mM, contractions induced by Ca2+ up to 5 mM, including 0 Ca2+, were increased with respect to those obtained in the presence of 1 mM EGTA. Basal 45Ca2+ uptake was not modified with Bay K 8644 (10(-6) M) or nifedipine (10(-6) M). K+ (25 and 50 mM) produced an increase on 45Ca2+ uptake, which was potentiated by Bay K 8644 (10(-6) M) and antagonized by nifedipine (10(-6) M); this latter agent reduced the potentiation elicited by the Ca2+ agonist.(ABSTRACT TRUNCATED AT 250 WORDS)

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / pharmacology*
  • Calcium / pharmacokinetics
  • Calcium / physiology*
  • Calcium Channel Blockers / pharmacology*
  • Cerebral Arteries / drug effects
  • Cerebral Arteries / physiology*
  • Humans
  • In Vitro Techniques
  • Muscle, Smooth, Vascular / drug effects
  • Muscle, Smooth, Vascular / metabolism
  • Muscle, Smooth, Vascular / physiology*
  • Nifedipine / pharmacology
  • Vasoconstrictor Agents / pharmacology*
  • Verapamil / pharmacology

Substances

  • Calcium Channel Blockers
  • Vasoconstrictor Agents
  • 3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester
  • Verapamil
  • Nifedipine
  • Calcium