Park_2002_Biochemistry_41_5588

Reference

Title : Cooperativity and oligomeric status of cardiac muscarinic cholinergic receptors - Park_2002_Biochemistry_41_5588
Author(s) : Park PS , Sum CS , Pawagi AB , Wells JW
Ref : Biochemistry , 41 :5588 , 2002
Abstract :

Muscarinic cholinergic receptors can appear to be more numerous when labeled by [(3)H]quinuclidinylbenzilate (QNB) than by N-[(3)H]methylscopolamine (NMS). The nature of the implied heterogeneity has been studied with M(2) receptors in detergent-solubilized extracts of porcine atria. The relative capacity for [(3)H]NMS and [(3)H]QNB was about 1 in digitonin-cholate, 0.56 in cholate-NaCl, and 0.44 in Lubrol-PX. Adding digitonin to extracts in cholate-NaCl increased the absolute capacity for both radioligands, and the relative capacity increased to near 1. The latency cannot be attributed to a chemically impure radioligand, instability of the receptor, an irreversible effect of NMS, or a failure to reach equilibrium. Binding at near-saturating concentrations of [(3)H]QNB in cholate-NaCl or Lubrol-PX was blocked fully by unlabeled NMS, which therefore appeared to inhibit noncompetitively at sites inaccessible to radiolabeled NMS. Such an effect is inconsistent with the notion of functionally distinct, noninterconverting, and mutually independent sites. Both the noncompetitive effect of NMS on [(3)H]QNB and the shortfall in capacity for [(3)H]NMS can be described quantitatively in terms of cooperative interactions within a receptor that is at least tetravalent; no comparable agreement is possible with a receptor that is only di- or trivalent. The M(2) muscarinic receptor therefore appears to comprise at least four interacting sites, presumably within a tetramer or larger array, and ligands appear to bind in a cooperative manner under at least some conditions.

PubMedSearch : Park_2002_Biochemistry_41_5588
PubMedID: 11969420

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Citations formats

Park PS, Sum CS, Pawagi AB, Wells JW (2002)
Cooperativity and oligomeric status of cardiac muscarinic cholinergic receptors
Biochemistry 41 :5588

Park PS, Sum CS, Pawagi AB, Wells JW (2002)
Biochemistry 41 :5588