Flynn_1989_Eur.J.Pharmacol_172_363

Reference

Title : Agonist binding to M1 muscarinic receptors is sensitive to guanine nucleotides - Flynn_1989_Eur.J.Pharmacol_172_363
Author(s) : Flynn DD , Palermo N , Suarez A
Ref : European Journal of Pharmacology , 172 :363 , 1989
Abstract :

Putative M1 (high-affinity pirenzepine) muscarinic receptors in rabbit hippocampal membranes, treated with 0.1 mM N-ethylmaleimide (NEM), were selectively labeled with [3H]pirenzepine. A single class of binding sites was labeled with a Kd of 3.4 nM, consistent with the pharmacologically-defined M1 subtype of muscarinic receptors. While full muscarinic agonists bound to high- and low-affinity states of [3H]pirenzepine-labeled M1 sites with a KL/KH ratio of approximately 100, the ratio for partial muscarinic agonists was approximately 10. The high-affinity binding of all agonists tested required divalent cations, and was interconverted to low-affinity binding in the presence of the non-hydrolyzable GTP analogue, guanylyl imidodiphosphate (GppNHp). Direct labeling of the high-affinity agonist state of M1 receptors was achieved with 5 nM [3H]oxotremorine-M by selectively uncoupling the high-affinity agonist state of M2 (low-affinity pirenzepine) receptors with NEM. The rate of dissociation of [3H]Pxotremorine-M from M1 receptors was accelerated 6-fold by GppNHp. These results provide further evidence which suggests that putative M1 muscarinic receptors activate second messenger systems by coupling to NEM-insensitive guanine nucleotide-binding proteins.

PubMedSearch : Flynn_1989_Eur.J.Pharmacol_172_363
PubMedID: 2583247

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Citations formats

Flynn DD, Palermo N, Suarez A (1989)
Agonist binding to M1 muscarinic receptors is sensitive to guanine nucleotides
European Journal of Pharmacology 172 :363

Flynn DD, Palermo N, Suarez A (1989)
European Journal of Pharmacology 172 :363