AJP - Endocrinology and Metabolism, Vol 263, Issue 3 E481-E488, Copyright © 1992 by American Physiological Society
Inhibitors of Na(+)-H+ exchange block stimulus-provoked pineal melatonin synthesis
A. K. Ho and C. L. Chik
Department of Physiology, University of Alberta, Edmonton, Canada.
In rat pinealocytes, amiloride can modulate adrenergic-stimulated cyclic
nucleotide accumulation. In this study, the effect of amiloride on
melatonin production was characterized. Addition of
5-(N,N-hexamethylene)amiloride, a potent inhibitor of the Na(+)-H+
antiport, dose dependently inhibited norepinephrine- and
isoproterenol-stimulated N-acetyltransferase (NAT) activity and melatonin
production. Similar inhibition was also observed when pineal melatonin
synthesis was stimulated directly with forskolin or dibutyryl adenosine
3',5'-cyclic monophosphate (cAMP), suggesting that the site of inhibition
is distal to cAMP accumulation. Similarities between the inhibitory
potencies of amiloride derivatives on the Na(+)-H+ antiport and pineal
melatonin synthesis indicate that the observed inhibition on pineal
melatonin synthesis by amilorides may be secondary to their actions on the
Na(+)-H+ antiport. Further studies also indicate that the inhibitory effect
of amilorides was not secondary to its cytotoxic actions and that
amilorides had no direct antagonistic action on NAT activity. Our findings,
therefore, suggest that, in addition to their effects on cyclic nucleotide
accumulation, the Na(+)-H+ antiport also plays an important role in the
cAMP-mediated melatonin synthesis in the rat pineal gland.
