Interaction of agonists and selective antagonists with gastric smooth muscle muscarinic receptors
| Autor: | F. D. Romano, Thomas W. Honeyman, Cheryl R. Scheid, P. A. Lucchesi, H. Yamaguchi |
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| Rok vydání: | 2004 |
| Předmět: |
Agonist
medicine.medical_specialty medicine.drug_class Adamantane In Vitro Techniques Biology Internal medicine Muscarinic acetylcholine receptor medicine Oxotremorine Animals Virulence Factors Bordetella Receptor Pharmacology Adenosine Diphosphate Ribose Stomach Parasympatholytics Muscarinic acetylcholine receptor M3 Muscarinic antagonist Muscle Smooth Muscarinic acetylcholine receptor M2 Pirenzepine General Medicine Receptors Muscarinic Quinuclidinyl Benzilate Endocrinology Parasympathomimetics Pertussis Toxin Biophysics Bufo marinus Folic Acid Antagonists Guanosine Triphosphate medicine.drug |
| Zdroj: | Naunyn-Schmiedeberg's Archives of Pharmacology. :145-151 |
| ISSN: | 1432-1912 0028-1298 |
| DOI: | 10.1007/bf00165136 |
| Popis: | The interaction of cholinergic agonists and antagonists with smooth muscle muscarinic receptors has been investigated by measurement of displacement of the muscarinic antagonist [3H]QNB (quinuclidinyl benzilate) in membranes prepared from toad stomach. The binding of [3H]QNB was saturable, reversible and of high affinity (KD = 423 pM). The muscarinic receptor subtypes present in gastric smooth muscle were classified by determining the relative affinities for the selective antagonists pirenzepine (M1), AF-DX 116 (M2) and 4-DAMP (M3). The results from these studies indicate the presence of a heterogeneous population of muscarinic receptor subtypes, with a majority (88%) exhibiting characteristics of M3 receptors and a much smaller population (12%) exhibiting characteristics of M2 receptors. The binding curve for the displacement of [3H]QNB binding by the agonist oxotremorine was complex and was consistent with presence of two affinity states: 24% of the receptors had a high affinity (KD = 4.7 nM) for oxotremorine and 76% displayed nearly a 1,000-fold lower affinity (KD = 4.4 μM). When oxotremorine displacement of [3H]QNB binding was determined in the presence GTPγS, high affinity binding was abolished, indicating that high affinity agonist binding may represent receptors coupled to G proteins. Moreover, pertussis toxin pretreatment of membranes also abolished high affinity agonist binding, indicating that the muscarinic receptors are coupled to pertussis toxin-sensitive G proteins. Reaction of smooth muscle membranes with pertussis toxin in the presence [32P]NAD caused the [32P]-labelling of a 40 kD protein that may represent the α subunit(s) of G proteins that are known to be NAD-ribosylated by the toxin. We conclude that both M3 and M2 receptors may be coupled to G proteins in a pertussis-sensitive manner. |
| Databáze: | OpenAIRE |
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