Endogenous dopamine regulates phosphate reabsorption but not NaK-ATPase in spontaneously hypertensive rat kidneys.

Abstract

Dopamine's modulatory actions on signal transduction in the spontaneously hypertensive rat (SHR) proximal tubule are blunted; therefore, it was predicted that dopamine does not regulate phosphate (Pi) reabsorption in SHR. To test this hypothesis, dopamine production was inhibited with carbidopa (10 mg/kg ip) 18 h before and during clearance measurements of chronically denervated SHR and Wistar-Kyoto (WKY) rat kidneys. Dopamine excretion decreased 80% from SHR and 85% from WKY rats. Pi excretion decreased 60 to 67%. Plasma Pi and calcium, inulin clearance, and Na excretion did not change. Citrate excretion, which reflects proton secretion by proximal tubules, decreased 72% from WKY rats. Citrate excretion was significantly lower from SHR (5 +/- 10 pmol/min) than from WKY rats (73 +/- 11 pmol/min) and was not altered by carbidopa. Carbidopa, injected 18 and 1 h before kidneys were collected, increased NaK-ATPase in cortical basolateral membranes from WKY rats (27%) but not in membranes from SHR. After the incubation of renal cortical minceates for 15 min with L-DOPA (10(-5) M), there was no change in brush border membrane vesicle uptake of 32Pi, (3H)glucose, or (14C)citrate. Incubation with carbidopa (10(-4) M) increased 32Pi uptake by 11% (P < 0.001) and (3H)glucose uptake by 9% (P = 0.02). (14C)citrate uptake was not increased by carbidopa but was higher in SHR (977 +/- 2 pmol/10 s.mg) than in WKY rats (823 +/- 43 pmol/10 s.mg; P = 0.04). In summary, dopamine produced in WKY rat and SHR proximal tubules decreases Pi uptake by using a signaling process distinct from those that regulate NaK-ATPase and the antiporter.(ABSTRACT TRUNCATED AT 250 WORDS)

Review on allosteric modulators of dopamine receptors so far

“…This is because of their capability to modulate cellular responses to a neurotransmitter dopamine with several important functions in the CNS and the PNS 22 . Dopamine works through its respective GPCRs to activate or attenuate reward mechanisms, motor function, central processing, and other physiologic activities 22,23 …”

“… 22 Dopamine works through its respective GPCRs to activate or attenuate reward mechanisms, motor function, central processing, and other physiologic activities. 22 , 23 …”

“…However, in D2‐like receptors the D2 and D3 receptors have a 75%, and the D2 and D4 receptors have a 53% shared identity in the transmembrane domains. 23 , 24 , 25 , 26 From these five dopamine receptors, D1 and D2 are the most widely studied subtypes due to their significant functions in reward, motor activity and their greater expression level. 26 , 27 , 28 …”

“…22 Dopamine works through its respective GPCRs to activate or attenuate reward mechanisms, motor function, central processing, and other physiologic activities. 22,23 Based on the molecular characteristic's dopamine receptors are receptors share an 80% identity in their transmembrane domains.…”

“…However, in D2-like receptors the D2 and D3 receptors have a 75%, and the D2 and D4 receptors have a 53% shared identity in the transmembrane domains. [23][24][25][26] From these five dopamine receptors, D1 and D2 are the most widely studied subtypes due to their significant functions in reward, motor activity and their greater expression level. [26][27][28] Although some current marketed dopaminergic drugs potentially have D1 activity, 29,30 utmost available medicines substantially target D2/D3 receptors.…”