Insulin increases D5 dopamine receptor expression and function in renal proximal tubule cells from Wistar-Kyoto rats.
BACKGROUND
Ion transport in the renal proximal tubule (RPT) is regulated by numerous hormones and humoral factors, including insulin and dopamine. Previous studies show an interaction between insulin and the D(1) receptor. Because both D(1) and D(5) receptors belong to the D(1)-like receptor subfamily, it is possible that an interaction between insulin and the D(5) dopamine receptor exists in RPT cells from normotensive Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHRs).


METHODS
D(5) receptor expression in immortalized RPT cells from WKY and SHRs was quantified by immunoblotting and D(5) receptor function by measuring Na(+)-K(+) ATPase activity.


RESULTS
Insulin increased the expression of the D(5) receptor. Stimulation with insulin (10(-7) mol/l) for 24 h increased D(5) receptor expression in RPT cells from WKY rats. This effect of insulin on D(5) receptor expression was aberrant in RPT cells from SHRs. The stimulatory effect of insulin on D(5) receptor expression in RPT cells from WKY rats was inhibited by a protein kinase C (PKC) inhibitor (PKC inhibitor peptide 19-31, 10(-6) mol/l) or a phosphatidylinositol 3 (PI3) kinase inhibitor (wortmannin, 10(-6) mol/l), indicating that both PKC and PI3 kinase were involved in the signaling pathway. Stimulation of the D(5) receptor heterologously expressed in HEK293 cells with fenoldopam (10(-7) mol/l/15 min) inhibited Na(+)-K(+) ATPase activity, whereas pretreatment with insulin (10(-7) mol/l/24 h) increased the D(5) receptor-mediated inhibition.


CONCLUSIONS
Insulin and D(5) receptors interact to regulate renal sodium transport; an aberrant interaction between insulin and D(5) receptor may participate in the pathogenesis of hypertension.
Yang
Jian
J
Department of Nutrition and Food Hygiene, The Third Military Medical University, Chongqing, People's Republic of China.
Cui
Zhigang
Z
He
Duofen
D
Ren
Hongmei
H
Han
Yu
Y
Yu
Changqing
C
Fu
Chunjiang
C
Wang
Zheng
Z
Yang
Chengming
C
Wang
Xukai
X
Zhou
Lin
L
Asico
Laureano D
LD
Villar
Van Anthony M
VA
Hopfer
Ulrich
U
Mi
Mantian
M
Zeng
Chunyu
C
Jose
Pedro A
PA
D000818:Animals; D002478:Cells, Cultured; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D007328:Insulin / Q000494:pharmacology*; D007687:Kidney Tubules, Proximal / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D011972:Receptor, Insulin / Q000378:metabolism; D050641:Receptors, Dopamine D5 / Q000187:drug effects / Q000502:physiology*; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D013268:Stimulation, Chemical
D007328:Insulin; D050641:Receptors, Dopamine D5; D011972:Receptor, Insulin; D000254:Sodium-Potassium-Exchanging ATPase