Dopamine-1 receptors in the proximal convoluted tubule of Dahl rats: defective coupling to adenylate cyclase.
We have previously reported a defect in the coupling of the renal dopamine-1 receptor (D1) to adenylate cyclase (AC) in the proximal convoluted tubule (PCT) of the spontaneously hypertensive rat (Okamoto-Aoki strain). To determine if this defect is present in another model of hypertension, we microdissected PCTs from Dahl salt-sensitive (DSS) and Dahl salt-resistant (DSR) rats on low- or high-NaCl diet. The ability of two selective D1 agonists, fenoldopam and SND-919-C12, and forskolin to stimulate AC activity in PCT was determined in each of the four groups of rats. Fenoldopam (10(-7) M) and SND-919-C12 (10(-6) M) failed to stimulate AC activity in the PCT of DSS rats whether on a low- or high-NaCl diet. In DSR rats, however, both fenoldopam and SND-919-C12 stimulated AC activity by 289-320% and 220-270%, respectively, whether on a low- or high-NaCl intake. Forskolin (10(-5) M), which directly stimulates AC activity, increased AC activity in all four groups. These studies show that in DSS rats the D1 receptor in the PCT fails to respond to D1 agonists. This defect is not a consequence of the hypertension because it was present in the DSS rats on a low-salt diet and before blood pressure elevation.
Ohbu
K
K
Department of Pediatrics, Kurume University School of Medicine, Japan.
Kaskel
F J
FJ
Kinoshita
S
S
Felder
R A
RA
D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D052160:Benzothiazoles; D001794:Blood Pressure / Q000187:drug effects; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D018491:Dopamine Agonists / Q000494:pharmacology; D005260:Female; D018818:Fenoldopam / Q000494:pharmacology; D006973:Hypertension / Q000378:metabolism*; D007687:Kidney Tubules, Proximal / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D000077487:Pramipexole; D051381:Rats; D011919:Rats, Inbred Strains; D017447:Receptors, Dopamine D1 / Q000819:agonists / Q000378:metabolism*; D012982:Sodium, Dietary / Q000494:pharmacology; D013844:Thiazoles / Q000494:pharmacology
D052160:Benzothiazoles; D018491:Dopamine Agonists; D017447:Receptors, Dopamine D1; D012982:Sodium, Dietary; D013844:Thiazoles; D005576:Colforsin; D000077487:Pramipexole; D000242:Cyclic AMP; D000262:Adenylyl Cyclases; D018818:Fenoldopam