Regulation of cyclic AMP levels by calcium in bovine adrenal medullary cells

J Neurochem. 1991 Nov;57(5):1721-8. doi: 10.1111/j.1471-4159.1991.tb06373.x.

Abstract

Both nicotine and histamine have been reported to increase cyclic AMP levels in chromaffin cells by Ca(2+)-dependent mechanisms. The present study investigated whether Ca2+ was an adequate and sufficient signal for increasing cyclic AMP in cultured bovine adrenal medullary cells. Depolarization with 50 mM K+ caused a two- to three-fold increase in cellular cyclic AMP levels over 5 min, with no change in extracellular cyclic AMP. This response was abolished by omission of extracellular Ca2+ and by 100 microM methoxyverapamil, and was unaffected by 1 microM tetrodotoxin and by 1 mM isobutylmethylxanthine. Veratridine (40 microM) also increased cellular cyclic AMP levels by two- to fourfold. This response was abolished by either methoxyverapamil or tetrodotoxin. The Ca2+ ionophore A23187 (10-50 microM) had little or no effect on cellular cyclic AMP levels. When the concentration of K+ used to depolarize the cells was reduced to 12-15 mM, the catecholamine release was similar to that induced by 50 microM A23187, and the cyclic AMP response was almost abolished. The results suggest that Ca2+ entry into chromaffin cells is a sufficient stimulus for increasing cellular cyclic AMP production. The possible involvement of a Ca2+/calmodulin-dependent isozyme of adenylate cyclase is discussed.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 1-Methyl-3-isobutylxanthine / pharmacology
  • Adrenal Medulla / drug effects
  • Adrenal Medulla / metabolism*
  • Adrenal Medulla / physiology
  • Animals
  • Calcimycin / pharmacology
  • Calcium / pharmacology
  • Calcium / physiology*
  • Cattle
  • Cells, Cultured
  • Cyclic AMP / metabolism*
  • Epinephrine / metabolism*
  • Kinetics
  • Norepinephrine / metabolism*
  • Potassium / pharmacology*
  • Tetrodotoxin / pharmacology
  • Veratridine / pharmacology

Substances

  • Calcimycin
  • Tetrodotoxin
  • Veratridine
  • Cyclic AMP
  • Potassium
  • Calcium
  • 1-Methyl-3-isobutylxanthine
  • Norepinephrine
  • Epinephrine