Comparison of the signaling mechanisms involved in the ETB receptor-mediated secretagogue action of endothelin-1 on dispersed zona glomerulosa cells and capsule-zona glomerulosa preparations of the rat adrenal gland.
Endothelin-1 (ET-1) is a hypertensive peptide, which is expressed in the rat adrenal gland, where it stimulates aldosterone secretion from zona glomerulosa (ZG) by activating the ETb receptor subtype. A higher effectiveness of ET-1 has been frequently observed when the integrity of adrenal tissue is preserved. Hence, we compared the aldosterone secretagogue action of ET-1 on dispersed rat ZG cells and capsule-ZG strips. ET-1 concentration-dependently raised aldosterone output by both preparations with similar potency. However, the efficacy of the maximal effective concentration of ET-1 (10-8 M) was about 2.7-fold higher in capsule-ZG strips. The ETb-receptor antagonist BQ-788 (10-7 M) abolished aldosterone response to 10-8 M ET-1 in both ZG preparations, while the ETa receptor antagonist BQ-123 was ineffective. The aldosterone secretagogue action of 10-8 M ET-1 on dispersed ZG cells was concentration-dependently suppressed by the protein kinase (PK) inhibitor calphostin-C. Conversely, both calphostin-C and the nitric oxide (NO) synthase (NOS) inhibitor NG-nitro-L-arginine methyl ester (L-NAME) evoked a concentration-dependent partial reversal of the aldosterone response to 10-8 M ET-1 of capsule-ZG strips. The NO donor L-arginine enhanced basal aldosterone yield of capsular strips, but not dispersed ZG cells. The PKA, cyclooxygenase and lipoxygenase inhibitors H-89, indomethacin and phenidone, as well as the beta-adrenoceptor antagonist l-alprenolol, were ineffective. Collectively, these findings allow us to conclude that in the rat i) the ETb receptor-mediated PKC activation is the main signaling mechanism involved in the direct stimulatory effect of ET-1 on ZG cells; and ii) the higher responsiveness of capsular strips to ET-1 may be accounted for by the ETb receptor-mediated release by stromal elements of NO, which in turn increases aldosterone secretion from ZG cells in a paracrine manner.
Rebuffat
P
P
Department of Human Anatomy and Physiology, Section of Anatomy, University of Padua, I-35121 Padua, Italy.
Macchi
C
C
Malendowicz
L K
LK
Nussdorfer
G G
GG
D000311:Adrenal Glands / Q000378:metabolism*; D000450:Aldosterone / Q000494:pharmacology; D000818:Animals; D001120:Arginine / Q000494:pharmacology; D002478:Cells, Cultured; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1 / Q000494:pharmacology*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009281:Naphthalenes / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin / Q000378:metabolism*; D015398:Signal Transduction; D015384:Zona Glomerulosa / Q000378:metabolism*
D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1; D009281:Naphthalenes; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin; D000450:Aldosterone; D001120:Arginine; C058819:calphostin C; D019331:NG-Nitroarginine Methyl Ester