Pg. Andreis et al., Guanylin: A novel regulatory peptide possibly involved in the control of Ca2+-dependent agonist-stimulated aldosterone secretion in rats, INT J MOL M, 3(1), 1999, pp. 59-62
Guanylin is a 15-amino acid peptide, which activates guanylate cyclase (GC)
and plays a major role in the regulation of water and electrolyte secretio
n by intestinal mucosa. The expression of guanylin prohormone has been rece
ntly demonstrated in the rat adrenal gland, and this prompted us to investi
gate whether guanylin, like other peptides secreted by adrenal medulla, aff
ects the function of the adrenal cortex. Autoradiography demonstrated the p
resence of [I-125]guanylin binding sites in the zona glomerulosa (ZG), but
not zona fasciculata-reticularis. Guanylin did not change either basal or A
CTH-stimulated steroid secretion of dispersed rat adrenocortical cells, but
concentration-dependently (from 10(-10) M to 10(-8) M) inhibited aldostero
ne response of ZG (capsular) cells to both angiotensin-II (ANG-II) and K+.
Guanylin (10(-8) M) blocked the aldosterone secretagogue effect of the Ca2-channel activator BAYK-8644, and the Ca2+-ionophore ionomycin counteracted
the inhibitory action of this peptide on the secretory responses of capsul
ar cells to ANG-II and K+. As expected, guanylin did not affect cyclic-AMP
release by capsular cells, but evoked a sizeable increase in cyclic-GMP pro
duction. Both the inhibitor of GMP synthase decoyinine and the GC-inhibitor
LY-83583, although suppressing cyclic GMP release, did not affect guanylin
-evoked inhibition of K+-stimulated aldosterone secretion. Collectively, th
ese findings allow us to conclude that guanylin: i) inhibits aldosterone se
cretion of rat ZG cells by interfering with the agonist-induced activation
of voltage-gated Ca2+-channels, the stimulation of guanylate cyclase concei
vably playing a negligible role; and ii) could be included in that group of
regulatory peptides, secreted by medullary chromaffin cells, which are abl
e to counteract an exceedingly high aldosterone secretion.