M. Torres et al., POSSIBLE ROLE OF NITRIC-OXIDE IN CATECHOLAMINE SECRETION BY CHROMAFFIN CELLS IN THE PRESENCE AND ABSENCE OF CULTURED ENDOTHELIAL-CELLS, Journal of neurochemistry, 63(3), 1994, pp. 988-996
We studied the effect of cultured endothelial cells on the secretion o
f catecholamines by cultured bovine chromaffin cells. Chromaffin cell
catecholamine secretion was stimulated by either boluses of potassium
(K+) or the nicotinic agonist 1,1-dimethyl-4-phenylpiperazinium (DMPP)
. Endothelial cells inhibited the catecholamine release and stimulator
y effects of K+ and DMPP. This inhibition increased with time, and in
25 min the initial stimulated secretory response (100%) to 30 mM K+ or
25 mu M DMPP dropped to 45 +/- 3% and 53.5 +/- 2.3%, respectively. Th
is endothelial cell-induced inhibition was blocked by the nitric oxide
synthase inhibitors N-nitro-L-arginine methyl ester (L-NAME) and N-mo
noethyl-L-arginine (L-NMMA), and by the guanylate cyclase inhibitor me
thylene blue, indicating that the L-arginine/nitric oxide/ cyclic GMP
pathway is involved in this endothelial cell-chromaffin cell interacti
on. In the absence of endothelial cells, incubation of chromaffin cell
s with L-NAME, LNMMA, or methylene blue also augmented the secretagogu
e-induced catecholamine secretion, indicating that nitric oxide from c
hromaffin cells could be implicated in an autoinhibitory process of ca
techolamine release. These results provide indirect evidence for the p
resence of nitric oxide synthase in bovine adrenomedullary chromaffin
cells. Our results show that there is an autoinhibitory mechanism of c
atecholamine release in chromaffin cells and that an additional level
of inhibition is observed when cultured vascular endothelial cells are
present. These two inhibitory processes may have different origins, b
ut they appear to converge into a common pathway, the L-arginine/nitri
c oxide synthase/guanylate cyclase pathway.