Characterization of alpha 2-adrenoceptors in the rat: proximal tubule, renal membrane and whole kidney studies.
In the present study, alpha 2-adrenoceptors have been characterized in rat renal proximal tubules which were isolated by a Percoll gradient technique. Competitive binding curves with [3H]rauwolscine (0.5 nM) and alpha 2-adrenoceptor agonists and antagonists were consistent with an alpha 2B-adrenoceptor subtype. However, the rank order of potency (Ki) for clonidine and UK 14,304 was reversed from that reported for other tissues (clonidine, 48 nM greater than UK 14,304, 330 nM). This rank order was confirmed in a crude renal membrane preparation consisting of whole kidney as well as separated medullary and cortical segments. An intrarenal infusion of clonidine at 11 nmol/kg per min resulted in a greater diuresis and natriuresis than an equimolar dose of UK 14,304 suggesting that clonidine also had a greater affinity in the collecting tubules. Further displacement studies in proximal tubules with [3H]rauwolscine and calcium channel blockers demonstrated that verapamil was the most potent (Ki, 2.3 microM), followed by diltiazem (48% displacement at 100 microM) and then nifedipine (no displacement at 100 microM). These studies indicated that alpha 2-adrenoceptor in the rat proximal tubule may be of the alpha 2B-adrenoceptor subtype. Further studies will be required to determine whether the reverse rank order of potency of clonidine and UK 14,304 is consistent with an alpha 2-adrenoceptor subtype which is different from that found in other tissue.
Stanko
C K
CK
Department of Internal Medicine, University of Manitoba, Winnipeg, Canada.
Vandel
M I
MI
Bose
R
R
Smyth
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DD
D000818:Animals; D001667:Binding, Competitive; D002121:Calcium Channel Blockers / Q000378:metabolism; D003000:Clonidine / Q000494:pharmacology; D066298:In Vitro Techniques; D007668:Kidney / Q000378:metabolism*; D007677:Kidney Function Tests; D007687:Kidney Tubules, Proximal / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D008566:Membranes / Q000378:metabolism; D011869:Radioligand Assay; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects / Q000378:metabolism*; D015016:Yohimbine / Q000378:metabolism
D002121:Calcium Channel Blockers; D011942:Receptors, Adrenergic, alpha; D015016:Yohimbine; D003000:Clonidine