Influence of 5′-(N′-Ethylcarboxanlido) Adenosine on Catecholarnine Secretion Evoked by Cholinergic Stimulation and Membrane Depolarization in the Rat Adrenal Gland

The present study was attempted to determine the effect of 5'-(N'-ethylcarboxamido) adenosine (NECA), which is an potent $A_2$-adenosine receptor agonist, on catecholamine (CA) secretion evoked by cholinergic stimulation, membrane depolarization and calcium mobilization from the isolated perfused rat adrenal gland. NECA (20 nM) perfused into the adrenal vein for 60 min produced a time-related inhibition in CA secretion evoked by ACh (5.32x10$^{-3}$ M), high $K^{+}$(5.6x10$^{-2}$ M), DMPP (10$^{-4}$ M for 2 min), McN-A-343 (10$^{-4}$ M for 2 min), cyclopiazonic acid (10$^{-5}$ M for 4 min) and Bay-K-8644 (10$^{-5}$ M for 4 min). Also, in the presence of $\beta$,${\gamma}$-methylene adenosine-5'-triphosphate (MATP), which is also known to be a selective $P_{2x}$-purinergic receptor agonist, showed a similar inhibition elf CA release evoked by ACh, high potassium, DMPP, McN-A-343, Bay-K-8644 and cyclopiazonic acid. However, in adrenal glands preloaded with 20$\mu$M NECA for 20 min under the presence of 20$\mu$M 3-isobutyl-1-methyl-xanthine (IBMX), an adenosine receptors antagonist, CA secretory responses evoked by ACh, high potassium, DMPP, McN-A-343, Bay-K-8644 and cyclopiazonic acid were much recovered in comparison to the case of NECA-treatment only. Taken together, these results indicate that NECA causes the marked inhibition of CA secretion evoked by stimulation of cholinergic (both nicotinic and muscarinic) receptors as well as by membrane depolarization. This inhibitory effect may be mediated by inhibiting influx of extracellular calcium and release in intracellular calcium in the rat adrenomedullary chromaffin cells through the adenosine receptor stimulation. Therefore, it is suggested that the inhibitory mechanism of adenosine receptor stimulation may play a modulatory role in regulating CA secretion.n.n.