Characterization of muscarinic receptors in rat kidney
| Autor: | Yvonne J.B. Van Megen, W. Matthijs Blankesteijn, Jaap F. Rodrigues de Miranda, Helene L.M. Siero, Frans G. M. Russel |
|---|---|
| Rok vydání: | 1993 |
| Předmět: |
Male
medicine.medical_specialty Population In Vitro Techniques Kidney Binding Competitive Amiloride chemistry.chemical_compound Internal medicine Muscarinic acetylcholine receptor medicine Methoctramine Animals Rats Wistar education Receptor Pharmacology education.field_of_study Kidney metabolism Muscarinic acetylcholine receptor M3 Receptors Muscarinic Pirenzepine Rats Quinuclidinyl Benzilate Dissociation constant Kinetics Endocrinology Parasympathomimetics chemistry medicine.drug |
| Zdroj: | European Journal of Pharmacology: Molecular Pharmacology. 244:21-27 |
| ISSN: | 0922-4106 |
| Popis: | Muscarinic receptors in mammalian kidney seem to be involved in diuresis. In this study we give a detailed characterization of receptors in rat kidney. Specific binding of [3H](-)-quinuclidinylbenzilate ([3H]QNB) to membranes of rat kidney cortex was saturable and of high affinity. A dissociation constant of 0.063 +/- 0.003 nM and a receptor density of 1.46 +/- 0.07 pmol/g wet weight were obtained. The dissociation kinetics could be best described by assuming a mono-exponential function (k-1 = (0.52 +/- 0.1) x 10(-4) s-1). The binding of [3H]QNB reached a maximum in 60 min at 0.6 nM at 37 degrees C. Competition experiments with the enantiomers of benzetimide confirmed the muscarinic nature of the [3H]QNB binding sites. The inhibition constants of pirenzepine (0.23 +/- 0.02 microM), (+-)-hexahydrosiladifenidol (0.040 +/- 0.002 microM), AF-DX 116 (1.45 +/- 0.07 microM), methoctramine (1.67 +/- 0.02 microM) and gallamine (78 +/- 3 microM) classified this receptor as an M3 receptor. Inhibition of [3H]QNB binding by the agonists methylfurtrethonium, arecoline, isoarecoline methiodide, arecaidine propargyl ester and McN-A-343 displayed monophasic inhibition curves. With (+/-)-cis-2-methyl-4-dimethylaminomethyl-1,3- dioxolane methiodide in two out of four experiments a small (11%) population of high affinity agonist sites could be detected. The potassium sparing diuretic amiloride inhibited [3H]QNB binding (36 +/- 3 microM). Although in a way related to the amiloride binding site, the muscarinic receptors in rat kidney are unlikely to be the primary target of diuretic action of this drug. |
| Databáze: | OpenAIRE |
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