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.