-Melanocyte-stimulating hormone-induced inhibition of angiotensin II receptor-mediated events in the rat adrenal zona glomerulosa

Abstract

It is well established that ACTH and angiotensin II (Ang II) stimulate aldosterone secretion from rat adrenal zona glomerulosa cells in vitro and mediate their steroidogenic effects via the cyclic AMP (cAMP) pathway and phosphoinositide turnover respectively. alpha-MSH also stimulates aldosterone secretion from zona glomerulosa cells in vitro, and recent studies from our laboratory have shown that its steroidogenic effects are mediated by increases in inositol 1,4,5-trisphosphate (IP3) production. alpha-MSH also stimulates adenylyl cyclase activity, but only at concentrations that are supramaximal for stimulation of steroidogenesis. The observation that alpha-MSH-stimulated IP3 accumulation declines as the activity of adenylyl cyclase increases prompted further studies on the interactions of cAMP and phosphoinositide production. The effects of alpha-MSH and ACTH on Ang II-stimulated steroidogenesis and IP3 accumulation were studied. On addition of increasing concentrations of ACTH, both the aldosterone and IP3 responses to Ang II were significantly inhibited; however, only high concentrations of alpha-MSH achieved this effect. These results suggest that cAMP or a cAMP-dependent event is able to inhibit phospholipase C activity. This hypothesis was tested by measuring IP3 production in Ang II-stimulated zona glomerulosa cells exposed to two different concentrations of alpha-MSH: 1 nmol/l, which stimulates the generation of IP3, and 1 mumol/l, which activates adenylyl cyclase. It was found that this high concentration of alpha-MSH significantly inhibited Ang II-stimulated aldosterone secretion and IP3 levels. In addition, alpha-MSH reduced 125I-labelled Ang II binding to rat adrenal zona glomerulosa cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Bacterial lipopolysaccharide (LPS) and interleukin 1 (IL-1) exert multiple physiological effects in the tilapia Oreochromis mossambicus (Teleostei)

“…This might be a general I* lenomenon for steroid-producing tissues, since the gonadotropin sensitivity of ovarian steroidogenesis is also inhibited by IL-1 (Hurwitzet al 1991). Interesting ly the LPS effect observed in the present study was specific for ACTH, which is compatible with the idea tiiat a-MSH and ACTH act via different mechanisms on teleost corticosteroid production, as in mammals Kapas et al 1992).…”

Local production and action of adrenomedullin in the rat adrenal zona glomerulosa

“…We found that adrenomedullin inhibited the increase in inositol phosphate turnover stimulated by angiotensin II, but the aldosterone response to angiotensin II in the presence of adrenomedullin did not differ significantly from that to angiotensin II alone (although it was lower than the response to adrenomedullin alone). The actions of adrenomedullin on inositol trisphosphate production and the response to angiotensin II closely resemble the actions of ACTH, a known adrenocortical stimulant, well recognized to act through cAMP (Kapas et al 1994). The results of the present study, however, do not exclude the possibility that adrenomedullin may alter intracellular Ca 2+ concentrations by a mechanism independent of inositol trisphosphate, as has been suggested by others (Yamaguchi et al 1995, Andreis et al 1997.…”

“…There is evidence both for the production of adrenomedullin by the zona glomerulosa and for the presence of specific receptors; in addition, a clear biological effect of adrenomedullin on zona glomerulosa function has been demonstrated. In several respects, the actions of adrenomedullin on the rat zona glomerulosa resemble the actions of ACTH: both peptides stimulate aldosterone and cAMP release, with the well-recognized order-of-magnitude difference in the dose-response curves (Kapas et al 1992); the actions of both peptides are attenuated by a PKA inhibitor; and neither peptide has an additive effect with angiotensin II (Kapas et al 1994). However, the physiological role of adrenomedullin in the rat zona glomerulosa requires elucidation.…”

Aldosterone secretion by the rat adrenal cortex is stimulated by the activation of protease-activated receptor 1

“…Adenylyl cyclase activity was measured by competitive radioligand binding, using a binding protein prepared from bovine adrenal glands, as described previously (Kapas et al 1994). IP 3 turnover was assessed using an adaptation of existing methods (Kapas et al 1994), as follows.…”

“…IP 3 turnover was assessed using an adaptation of existing methods (Kapas et al 1994), as follows. Briefly, rat adrenal capsules were obtained as described above.…”