Paradoxical inhibitory effect of cromakalim on sup 86 Rb outflow from pancreatic islet cells

Journal Article · Sat Dec 01 00:00:00 EST 1990 · Journal of Pharmacology and Experimental Therapeutics; (USA)

OSTI ID:5989098

Lebrun, P; Antoine, M H; Devreux, V; Hermann, M; Herchuelz, A ^[1]

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1. Free Univ. of Brussels (Belgium)

Cromakalim appears to be the most potent pharmacologic agent belonging to the new class of smooth muscle relaxants: the K+ channel openers. The present study aimed at characterizing the effects of cromakalim on 86Rb outflow, 45Ca outflow and insulin release from prelabeled and perifused rat pancreatic islets. Cromakalim provoked a concentration-dependent reduction in 86Rb outflow. This inhibitory effect was attenuated in islets exposed throughout to glibenclamide or to a Ca+(+)-free medium. In islets exposed to glucose and extracellular Ca++, cromakalim induced a dose-dependent reduction in 45Ca outflow. The drug also inhibited the increase in 45Ca outflow mediated by K+ depolarization. Lastly, cromakalim elicited a concentration-dependent inhibition of insulin release from islets perifused in the presence of glucose and extracellular Ca++. The present data suggest that the paradoxical inhibitory effect of cromakalim on 86Rb outflow probably reflects the capacity of the drug to reduce the activity of the ATP-sensitive K+ channels and to indirectly inhibit the Ca+(+)-activated K+ channels. Furthermore, the cromakalim-induced changes in 45Ca outflow are compatible with an inhibitory effect of the drug on the voltage-dependent Ca++ channels.

• OSTI ID: 5989098
• Journal Information: Journal of Pharmacology and Experimental Therapeutics; (USA), Vol. 255:3; ISSN 0022-3565
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
INSULIN
SECRETION
VASODILATORS
BIOLOGICAL EFFECTS
CALCIUM 45
CALCIUM COMPOUNDS
DOSE-RESPONSE RELATIONSHIPS
GLUCOSE
INHIBITION
MUSCLES
PANCREAS
PERFUSED ORGANS
POTASSIUM COMPOUNDS
RATS
RUBIDIUM 86
RUBIDIUM COMPOUNDS
ALDEHYDES
ALKALI METAL COMPOUNDS
ALKALI METAL ISOTOPES
ALKALINE EARTH ISOTOPES
ALKALINE EARTH METAL COMPOUNDS
ANIMALS
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
BODY
CALCIUM ISOTOPES
CARBOHYDRATES
CARDIOVASCULAR AGENTS
DAYS LIVING RADIOISOTOPES
DIGESTIVE SYSTEM
DRUGS
ENDOCRINE GLANDS
EVEN-ODD NUCLEI
GLANDS
HEXOSES
HORMONES
INTERMEDIATE MASS NUCLEI
ISOMERIC TRANSITION ISOTOPES
ISOTOPES
MAMMALS
MINUTES LIVING RADIOISOTOPES
MONOSACCHARIDES
NUCLEI
ODD-ODD NUCLEI
ORGANIC COMPOUNDS
ORGANS
PEPTIDE HORMONES
RADIOISOTOPES
RODENTS
RUBIDIUM ISOTOPES
SACCHARIDES
VERTEBRATES
550201* - Biochemistry- Tracer Techniques