The Adenosine Analogue N⁶‐L‐Phenylisopropyladenosine Inhibits Catecholamine Secretion from Bovine Adrenal Medulla Cells by Inhibiting Calcium Influx

Abstract

We reported earlier that adenine nucleotides and adenosine inhibit acetylcholine-induced catecholamine secretion from bovine adrenal medulla chromaffin cells. In this article, we used an adenosine analogue, N6-L-phenylisopropyladenosine (PIA), to study the mechanism underlying inhibition of catecholamine secretion by adenosine. PIA inhibits secretion induced by a nicotinic agonist, 1,1-dimethyl-4-phenylpiperazinium, or by elevated external K+. The half-maximal effect on 1,1-dimethyl-4-phenylpiperazinium-induced secretion occurred at approximately 5 x 10(-5) M. The inhibition is immediate and reversible. Fura-2 measurements of cytosolic free Ca2+ indicate that PIA inhibits Ca2+ elevation caused by stimulation; measurements of 45Ca2+ influx show that PIA inhibits uptake of Ca2+. PIA does not inhibit calcium-evoked secretion from digitonin-permeabilized cells, nor does PIA cause any significant change in the dependence of catecholamine secretion on calcium concentration. These data suggest that inhibition by PIA occurs at the level of the voltage-sensitive calcium channel.

The adrenergic stress response in fish: control of catecholamine storage and release

“…In the adrenal medulla of mammals, ATP co-released with catecholamines from chromaffin cells during exocytosis, is degraded to adenosine within the extracellular space [72]. Through an autocrine or paracrine pathway, adenosine, or adenosine agonists, can suppress catecholamine secretion from the adrenal medulla [51,52,151] via specific adenosine receptors on the surface of chromaffin cell [47]. Consequently, adenosine receptor blockade enhances the secretory response elicited by acetylcholine [151].…”

5′‐(N‐Ethylcarboxamido)adenosine Inhibits Ca2+ Influx and Activates a Protein Phosphatase in Bovine Adrenal Chromaffin Cells

“…We took advantage of the fact that adrenal chromaffin cells express selectively the A26 subtype of the adenosine receptor (Casad6 et al, 1992) to avoid A, effects of this nonspecific agonist . In fact, the effects of the A, agonist R-PIA on DMPP-evoked Ca 2+ influx (this study) and secretion (Chern et al ., 1992) could be seen only at high concentrations, at which this agent also binds to A2 receptors . Our results confirm the inhibitory effect of adenosine on the nicotinic-evoked CA secretion from chromaffin cells reported previously (Chern et al ., 1987) but differ from the previous data in several aspects .…”

“…Because CA secretion from chromaffin cells is tightly coupled to extracellular Ca 2+ influx (Kilpatrick et al ., 1982), it is reasonable to conclude that NECA-induced inhibition of CA release evoked by DMPP is due to the reduction by NECA of Ca 2+ entry activated by DMPP stimulation, as has been proposed to occur in brain (Fredholm and Dunwiddie, 1988 ;Miller, 1990) . Other alternative mechanisms involving direct effects on exocytotic machinery (Prince and Stevens, 1992;Scholz and Miller, 1992) are unlikely because secretion of CA from digitonin-permeabilized chromaffin cells is not affected by adenosine analogues (Chern et al, 1992) .…”

“…Thus, it is to be expected that the physiological effect of adenosine would be evident only at relatively high concentrations and would lead to cyclic AMP generation . However, both the effects of adenosine and adenosine agonists on CA secretion (Chern et al ., 1988(Chern et al ., , 1992 and adenosine transport (Delicado et al, 1990) are not associated with a modification of cyclic AMP levels in chromaffin cells . Thus, alternative signal transduction systems coupled to the A 2 adenosine receptor should be studied in chromaffin cells .…”

Functional distribution of Ca2+-coupled P2 purinergic receptors among adrenergic and noradrenergic bovine adrenal chromaffin cells

“…7). Finally, adenosine arising from the degradation of extracellular ATP may contribute to the inhibitory loop [48]. …”