Autoradiographic localization of dopamine D1 receptors in the human kidney.
The pharmacological profile and the anatomical localization of the selective D1-receptor antagonist [3H][R]-(+)-8-chloro-2,3,4,5-tetrahydro-5-phenyl-1H-3-benzazepin-7 -al- hemimaleate ([3H]SCH 23390) were studied in frozen sections of human kidney by using combined in vitro radioreceptor binding and autoradiographic techniques. [3H]SCH 23390 was bound by sections of human kidney in a manner consistent with the labeling of D1 sites, with a Kd value of 3.87 nM and with a Bmax value of 143 fmol/mg protein. Light microscope autoradiography revealed the highest density of [3H]SCH 23390 binding sites within the macula densa and the proximal tubules followed in descending order by the ascending limb of the loop of Henle, the distal tubules and the descending limb of the loop of Henle. No specific binding was noticeable within the glomeruli or within the epithelium of collecting tubules. [3H]SCH 23390 binding sites were also observed within the medial layer of intrarenal artery branches. These findings show that dopamine D1 receptor sites in the human kidney have a localization similar to that described in laboratory mammals with a higher density of tubular than of vascular receptors. The above data account for the vascular, diuretic and natriuretic effects elicited by D1 receptor stimulation in man.
Ricci
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A
Dipartimento di Scienze Cardiovascolari e Respiratorie, Università La Sapienza, Roma, Italy.
Escaf
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S
Vega
J A
JA
Amenta
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F
D000328:Adult; D000368:Aged; D001345:Autoradiography; D001552:Benzazepines / Q000378:metabolism; D006801:Humans; D007668:Kidney / Q000648:ultrastructure*; D007700:Kinetics; D008853:Microscopy; D008875:Middle Aged; D017447:Receptors, Dopamine D1 / Q000032:analysis*; D014316:Tritium
D001552:Benzazepines; D017447:Receptors, Dopamine D1; D014316:Tritium