Renal effects of intracerebroventricularly injected tachykinins in the conscious saline-loaded rat: receptor characterization

Abstract

1. The effects of intracerebroventricularly (i.c.v.) injected substance P (SP), neurokinin A (NKA) and [MePhe⁷]neurokinin B (NKB) were investigated on renal excretion of water, sodium and potassium in the conscious saline-loaded rat. The central effects of [MePhe⁷]NKB were characterized with selective tachykinin antagonists for NK₁ (RP 67580), NK₂ (SR 48968) and NK₃ (R 820) receptors.

2. Whereas SP or NKA (65 or 650 pmol) failed to modify the renal responses, [MePhe⁷]NKB (65–6500 pmol) produced dose-dependent and long-lasting (30–45 min) decreases in renal excretion of water (maximal reduction at 65 pmol: from 66.14±7.62 to 21.07±3.79 μl min⁻¹), sodium (maximal reduction at 65 pmol: from 10.19±2.0 to 1.75±0.48 μmol min⁻¹) and potassium (maximal reduction at 65 pmol: from 4.31±1.38 to 0.71±0.27 μmol min⁻¹). While 650 pmol [MePhe⁷]NKB elevated urinary osmolality, neither 65 pmol nor 6.5 nmol [MePhe⁷]NKB altered this parameter.

3. Both the antidiuresis and antinatriuresis induced by [MePhe⁷]NKB (65 pmol) were significantly blocked by the prior i.c.v. injection of R 820 (1.3 nmol, 5 min earlier), although the potassium excretion was only partially reduced. However, R 820 did not affect the antidiuresis and antinatriuresis elicited by endothelin-1 (1 pmol, i.c.v.). On its own, R 820 decreased renal potassium excretion with no effect on urinary osmolality and renal excretion of water and sodium. The i.c.v. co-injection of RP 67580 and SR 48968 (6.5 nmol each, 5 min earlier) failed to modify the renal responses to [MePhe⁷]NKB in a similar study.

4. The central effects of [MePhe⁷]NKB (65 pmol) on renal excretion were blocked by the prior i.v. administration of a linear peptide vasopressin V₂ receptor antagonist (50 μg kg⁻¹, 5 min earlier).

5. These results suggest that the central NK₃ receptor, probably located in the hypothalamus, is implicated in the renal control of water and electrolyte homeostasis through the release of vasopressin in the conscious saline-loaded rat.

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