Antagonistic actions of renal dopamine and 5-hydroxytryptamine: Increase in Na+, K+-ATPase activity in renal proximal tubules via activation of 5-HT1A receptors

• Type: Article in International Scientific Journal
• Date: 1996

Authors

soares-da-silva, p (Author) FMUP; Perpetua Pinto do O (Author) Other; Bertorello, AM (Author) Other

Journal

Title: British Journal of Pharmacology

Vol. 117

Pages: 1199-1203

ISSN: 0007-1188

Publisher: Wiley-Blackwell

Indexing

ISI Web of Knowledge - 22 Citations

Scopus - 24 Citations

Other information

Authenticus ID: P-001-EMW

Abstract (EN): 1 5-Hydroxytryptamine (5-HT) is antinatriuretic. Since this effect of 5-HT is not accomplished by changes in glomerular haemodynamics, we have examined in this study whether 5-HT may influence sodium excretion by affecting the Na+, K+-ATPase activity in renal cortical tubules. 2 Na+,K+-ATPase activity was determined as the rate of [P-32]-ATP hydrolysis in renal cortical tubules in suspension. Basal Na+,K+-ATPase activity in renal tubules was 4.8+/-0.4 mu mol Pi mg(-1) protein h(-1) (n=8). The 5-HT1A receptor agonist, (+/-)-8-hydroxy-2-(di-n-propylamino) tetraline (8-OH-DPAT) (10 to 3000 nM) induced a concentration-dependent increase (P<0.05) in Na+,K+-ATPase activity with an EC(50) value of 355 nM (95% confidence limits: 178, 708). Maximal stimulation elicited by 3000 nM of 8-OH-DPAT was antagonized by the selective 5-HT1A receptor antagonist, (+)-WAY 100135 (10 to 1000 nM) with an IC50 value of 20 nM (14, 29); 0.3 mu M (+)-WAY 100135 completely abolished (P<0.01) the stimulatory effect of 8-OH-DPAT. The stimulatory effect of 8-OH-DPAT was found to be time-dependent (15+/-2% and 66+/-7% increase at 2.5 and 5.0 min, respectively). The 5-HT2 receptor agonist alpha-methyl-5-HT (100 to 3000 nM) did not induce any significant changes in Na+,K+-ATPase activity (5.0+/-1.5 mu mol Pi mg(-1) protein h(-1); n=4). 3 The stimulatory effect 8-OH-DPAT was absent when homogenates were used. Stimulation occurred at a V-max concentration (70 mM) of sodium support:ng the notion that stimulation occurs independently of increasing sodium permeability. 4 The inhibitory effect of dopamine (P<0.05) on Na+,K+-A-TPase activity was blunted by co-incubation with 8-OH-DPAT (0.5 mu M). 5 It is concluded that activation of 5-HT1A receptors increases Na+,K+-ATPase activity in renal cortical tubules; this effect may represent an important cellular mechanism, at the tubule level, responsible for the antinatriuretic effect of 5-HT.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 5