5'-(N-ethylcarboxamido)adenosine inhibits Ca2+ influx and activates a protein phosphatase in bovine adrenal chromaffin cells

J Neurochem. 1995 Jan;64(1):77-84. doi: 10.1046/j.1471-4159.1995.64010077.x.

Abstract

We investigated the effect of the adenosine receptor agonist 5'-(N-ethylcarboxamido)adenosine (NECA) in catecholamine secretion from adrenal chromaffin cells that exhibit only the A2b subtype adenosine receptor. NECA reduced catecholamine release evoked by the nicotinic agonist 1,1-dimethyl-4-phenylpiperazinium (DMPP) in a time-dependent manner. Inhibition reached 25% after 30-40-min exposure to NECA. This effect on DMPP-evoked catecholamine secretion was mirrored by a similar (27.7 +/- 3.3%), slowly developing inhibition of [Ca2+]i transients induced by DMPP that peaked at 30-min preincubation with NECA. The capacity of the chromaffin cells to buffer Ca2+ load was not affected by the treatment with NECA. Short-term treatment with NECA failed both to modify [Ca2+]i levels and to increase endogenous diacylglycerol production, showing that NECA does not activate the intracellular Ca2+/protein kinase C signaling pathway. The inhibitory effects of NECA were accompanied by a 30% increase of protein phosphatase activity in chromaffin cell cytosol. We suggest that dephosphorylation of a protein involved in DMPP-evoked Ca2+ influx pathway (e.g., L-type Ca2+ channels) could be the mechanism of the inhibitory action of adenosine receptor stimulation on catecholamine secretion from adrenal chromaffin cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine / analogs & derivatives*
  • Adenosine / pharmacology
  • Adenosine-5'-(N-ethylcarboxamide)
  • Animals
  • Calcium / metabolism*
  • Catecholamines / metabolism
  • Cattle
  • Cells, Cultured
  • Chromaffin System / cytology*
  • Chromaffin System / enzymology
  • Chromaffin System / metabolism*
  • Dimethylphenylpiperazinium Iodide / pharmacology
  • Enzyme Activation / drug effects
  • Phosphoprotein Phosphatases / metabolism*
  • Phosphoprotein Phosphatases / physiology
  • Protein Kinase C / physiology
  • Time Factors
  • Vasodilator Agents / pharmacology*

Substances

  • Catecholamines
  • Vasodilator Agents
  • Adenosine-5'-(N-ethylcarboxamide)
  • Dimethylphenylpiperazinium Iodide
  • Protein Kinase C
  • Phosphoprotein Phosphatases
  • Adenosine
  • Calcium