J Pharmacol Exp Ther. 1990 Jan;252(1):293-9.

Imidazoline-guanidinium receptive site in renal proximal tubule: asymmetric distribution, regulation by cations and interaction with an endogenous clonidine displacing substance.

The Journal of pharmacology and experimental therapeutics

I Coupry, D Atlas, R A Podevin, I Uzielli, A Parini

PMID: 2153803

Abstract

In the present report we have used [3H]idazoxan to characterize the rabbit renal imidazoline preferring site by defining its plasmalemma distribution, its regulation by cations and the type of interaction with the clonidine displacing substance (CDS), a putative endogenous ligand for the imidazoline receptor. The density of [3H]idazoxan binding sites was 12-fold higher in purified basolateral membranes than in brush-border membranes (maximal binding activity, 566 +/- 118 vs. 46 +/- 2 fmol/mg of protein). In basolateral membranes, [3H]idazoxan binding was inhibited not only by imidazoline compounds but also by guanidinium analogs such as guanabenz, amiloride, 5-(M-ethyl-N-isopropyl)amiloride and phenamylamiloride. Amiloride had no effect on the dissociation rate of [3H]idazoxan, suggesting a direct interaction of this molecule with the ligand binding site. [3H]Idazoxan binding was 80% inhibited by 150 mM K+ or Rb+. The effect of K+ appeared to occur through the interaction with an allosteric site in as much as both the apparent dissociation constant and the dissociation rate of [3H]idazoxan were increased in the presence of 75 mM K+. CDS inhibited [3H]idazoxan binding with a half-maximal effective concentration of 2 U/250 microliters. The competitive nature of CDS effect was indicated by the increase in the apparent dissociation constant of [3H]idazoxan (Kd from 3 +/- 0.3 to 8.5 +/- 0.2 nM, P less than .01) in the presence of CDS. In conclusion, our findings showed that the imidazoline-guanidinium receptive site is located mainly in the basolateral side of the tubular cell, recognizes CDS and is regulated by K+.(ABSTRACT TRUNCATED AT 250 WORDS)

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Substances

• Dioxanes
• Dioxins
• Imidazoline Receptors
• Receptors, Adrenergic, alpha
• Receptors, Drug
• Yohimbine
• Amiloride
• clonidine-displacing substance
• Magnesium
• Clonidine
• Potassium
• Idazoxan

MeSH terms

• Amiloride / pharmacology
• Animals
• Binding Sites
• Clonidine / antagonists & inhibitors
• Clonidine / metabolism
• Dioxanes / metabolism
• Dioxins / metabolism
• Idazoxan
• Imidazoline Receptors
• In Vitro Techniques
• Kidney Tubules, Proximal / analysis
• Magnesium / pharmacology
• Male
• Potassium / pharmacology
• Rabbits
• Receptors, Adrenergic, alpha / analysis
• Receptors, Adrenergic, alpha / drug effects
• Receptors, Drug / analysis
• Yohimbine / metabolism

Publication Types

• Journal Article

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