Stimulatory effect of the substance P antagonist spantide-II on aldosterone secretion of dispersed rat zona glomerulosa cells.
Substance P (SP) did not affect either basal or agonist-stimulated aldosterone production by dispersed rat zona glomerulosa (ZG) cells. In contrast, the SP-receptor antagonist spantide-II (SPA), at 10(-8)/10(-6) M concentrations, markedly raised basal and 10(-9) M ACTH, but not 10(-9) M angiotensin II-stimulated aldosterone secretion. The secretagogue effect of 10(-6) M SPA was annulled by SP (10(-6) M) and the protein kinase (PK)-C inhibitor Ro31-8220 (10(-6) M), but was unaffected by the PKA inhibitor H-89 (10(-5) M). In light of these findings the following conclusions can be drawn: (i) SP does not exert a physiologically relevant direct modulatory action on aldosterone secretion of rat ZG cells; (ii) a receptor-independent inhibitory interaction is likely to occur between SP and SPA molecules; and (iii) SPA activates, through a receptor-independent mechanism, phosphoinositide signaling pathway in rat ZG cells.
Malendowicz
L K
LK
Department of Histology and Embryology, School of Medicine, Poznan, Poland.
Rebuffat
P
P
Nussdorfer
G G
GG
D000450:Aldosterone / Q000096:biosynthesis / Q000378:metabolism*; D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D001481:Basal Metabolism; D004353:Drug Evaluation, Preclinical; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D007211:Indoles / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D051381:Rats; D017208:Rats, Wistar; D012636:Secretory Rate / Q000187:drug effects; D013268:Stimulation, Chemical; D013373:Substance P / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D015384:Zona Glomerulosa / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism
D004791:Enzyme Inhibitors; D007211:Indoles; D000804:Angiotensin II; C065446:spantide II; D013373:Substance P; D000450:Aldosterone; D011493:Protein Kinase C; C064758:Ro 31-8220