In:
Canadian Journal of Physiology and Pharmacology, Canadian Science Publishing, Vol. 70, No. 7 ( 1992-07-01), p. 1016-1020
Abstract:
Norepinephrine stimulates renal tubular sodium reabsorption, probably through an α 1 -adrenoceptor-mediated mechanism. Although the distribution of α 1 -adrenoceptors in the kidney has been studied with autoradiography, the precise location of these receptors in isolated nephron segments is unclear. Using a microassay we determined the specific binding of [ 125 I]iodoarylazidoprazosin ([ 125 I]prazosin), a high specific radioactivity analog of the selective α 1 -antagonist prazosin, to microdissected glomeruli and tubule segments. Specific binding of [ 125 I]prazosin (3 nM) in the proximal convoluted tubule was time- and concentration-dependent, saturable, and reversible. In this segment the apparent K D by association and dissociation rate constants of [ 125 I]prazosin binding was 0.47 nM, and the maximum receptor density was ~ 0.19 fmol/mm, or 720 fmol/mg protein. Binding specificity was verified in competition studies with excess (3 μM) unlabeled prazosin and probes for α 2 - (yohimbine), β- (propranolol), dopamine 1 - (SCH23390), and dopamine 2 - (S-sulpiride) receptors. [ 125 I]Prazosin binding was inhibited significantly only by unlabeled prazosin. Mapping of prazosin binding along the nephron revealed that the highest density was in the proximal convoluted tubule, followed by the proximal straight tubule. Lesser binding was found in the thick ascending limb and in the distal convoluted tubule, whereas in the cortical and outer medullary collecting duct and in glomeruli, binding was not significantly different from zero. These results demonstrate specific prazosin binding sites in the proximal and early distal nephron where direct innervation by monoaminergic nerves is most abundant, and suggest that portions of the nephron beyond the proximal tubule, specifically the diluting segment, may also be under α 1 -agonist influence.Key words: α 1 -adrenoceptor, prazosin, isolated tubule, glomerulus, catecholamine.
Type of Medium:
Online Resource
ISSN:
0008-4212
,
1205-7541
Language:
English
Publisher:
Canadian Science Publishing
Publication Date:
1992
detail.hit.zdb_id:
2004356-9
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