The effect of the calcium channel agonist BAY K 8644 on the ability of KCl and norepinephrine to induce contractions of rabbit aortic rings has been examined in Krebs-Henseleit buffer containing either 4.0 or 6.8 mM potassium. BAY K 8644 (10-8 to 10-6 M) alone induced slowly developing aortic contractures which were 10 (at 4.0 mM potassium) or 20 (at 6.8 mM potassium) percent of the maximum obtainable with norepinephrine. These contractions were not observed in every experiment, but were more likely to occur at 6.8 mM (71% at 10-6 M BAY K 8644) when compared to 4.0 mM (31% at 10-6 M BAY K 8644) potassium buffer. BAY K 8644, in either potassium buffer, induced a statistically significant shift to the left in the norepinephrine dose-response curve. The norepinephrine dose-response curve was significantly curvilinear in the presence of 3 × 10-8 M BAY K 8644 (6.8 mM potassium) and 10-6 M BAY K 8644 (4.0 mM potassium). Similarly, BAY K 8644 induced sinistral shifts in the KCl dose-response curve with a curvilinear function observed at 3 × 10-7 M BAY K 8644. These data show that BAY K 8644 is capable of inducing aortic contractures at potassium concentrations significantly lower than previously reported. Furthermore, BAY K 8644 facilitates opening of calcium channels by either potassium or norepinephrine. In contrast to others, our data indicates that BAY K 8644 can effect calcium channels activated by norepinephrine. Finally, our data suggest that the alpha and dihydropyridine receptors are capable of interacting and that occupation of one receptor can affect the action of a compound binding to the other receptor.
|Number of pages||10|
|State||Published - Feb 24 1986|
Bibliographical noteFunding Information:
This work was supported by funds from the American Heart Association-Kentucky Affiliate. The authors would like to thank Dr. Frederick Hoffmeister, Bayer Pharmaceuticals, Wuppertal, West Germany for supplying us with BAY K 8644. We would also like to thank Dr. William R. Martin for his constructive comments during the course of these experiments and Joyce Anderson, Beth Estes and Deborah Turner for supervising the preparation of this manuscript.
ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology (all)
- Pharmacology, Toxicology and Pharmaceutics (all)