Inhibitory action of novel arginine derivative on catecholamine secretion evoked by acetylcholine from cultured bovine adrenal chromaffin cells

J Cardiovasc Pharmacol. 2003 Dec:42 Suppl 1:S15-8. doi: 10.1097/00005344-200312001-00005.

Abstract

A novel product, 4-amino-5-guanidinopentanoic acid 15-[(4-aminobutyl)-3-aminopropylcarbamoyl] pentadecyl ester (Arg-HSA-Spm), was synthesized based on ptilomycalin A, which is one of the extracts from marine sponge. Arg-HSA-Spm contains arginine in its chemical structure. The pharmacological action of Arg-HSA-Spm on catecholamine secretion from cultured bovine adrenal chromaffin cells was examined. Arg-HSA-Spm inhibited catecholamine secretion stimulated by the physiological secretagog acetylcholine. This inhibitory action of Arg-HSA-Spm on catecholamine secretion induced by 10(-4) M acetylcholine was dose-dependent from 10(-8) M to 10(-5) M. In the presence of 3 x 10(-7) M Arg-HSA-Spm, the stimulation of catecholamine secretion observed by increasing acetylcholine up to 10(-3) M did not reach the maximal level observed without Arg-HSA-Spm. Arg-HSA-Spm at 10(-5) M suppressed both the increase in intracellular free Ca2+ level and the influx of 45Ca2+ induced by 10(-4) M acetylcholine. The Arg-HSA-Spm-induced suppression of intracellular free Ca2+ level, the influx of 45Ca2+ and catecholamine secretion were not observed in the presence of extracellular K+ at 56 mM. The results presented in this study suggested that Arg-HSA-Spm may inhibit the influx of extracellular Ca2+ into the cells, probably through its blocking action related to acetylcholine receptors, resulting in the inhibition of catecholamine secretion in adrenal chromaffin cells.

MeSH terms

  • Acetylcholine / pharmacology*
  • Adrenal Medulla / cytology
  • Adrenal Medulla / drug effects
  • Adrenal Medulla / metabolism
  • Alkaloids / chemistry
  • Animals
  • Arginine / analogs & derivatives
  • Arginine / chemistry
  • Arginine / pharmacology*
  • Calcium / metabolism
  • Calcium Radioisotopes / metabolism
  • Carbamates / pharmacology*
  • Catecholamines / antagonists & inhibitors*
  • Catecholamines / metabolism*
  • Cattle
  • Cells, Cultured
  • Chromaffin Cells / drug effects*
  • Chromaffin Cells / metabolism*
  • Dose-Response Relationship, Drug
  • Guanidines
  • Spermidine / analogs & derivatives*
  • Spermidine / chemical synthesis
  • Spermidine / pharmacology*

Substances

  • 4-amino-5-guanidinopentanoic acid 15-((4-aminobutyl)-3-aminopropylcarbamoyl) pentadecyl ester
  • Alkaloids
  • Calcium Radioisotopes
  • Carbamates
  • Catecholamines
  • Guanidines
  • ptilomycalin A
  • guanidinospermidine
  • Arginine
  • Acetylcholine
  • Calcium
  • Spermidine