Heterogeneity of guinea-pig lung muscarinic receptors revealed by [3H]4-DAMP-binding.
Muscarinic receptors present in guinea-pig lung were characterized using the M3 selective radioligand [3H]4-diphenylacetoxy-N-methyl-piperidine methiodide ([3H]4-DAMP). In saturation studies, [3H]4-DAMP identified two populations of binding sites with approximately 4% of the sites displaying high affinity (Kd = 0.21 nM and Bmax = 10 fmol/mg prot.) while the remaining sites were low affinity ones (Kd = 18.11 nM and Bmax = 269 fmol/mg prot.). In competition studies with [3H]4-DAMP (0.35 nM), methoctramine and hexahydro-siladifenidol (HHSiD) identified 50 and 70% of high affinity binding sites displaying the pharmacological profile of the M2 and the M3 receptors, respectively. No evidence was found for high affinity [3H]pirenzepine binding sites in guinea-pig lung. However, pirenzepine/[3H]4-DAMP competition experiments suggested that pirenzepine recognized an equal proportion of [3H]4-DAMP binding sites with intermediate and low affinity binding constants. The intermediate affinity binding constant was inconsistent with the presence of M1 receptors and reflected more the presence of M4 or a mixture of M3 and M4 receptors. The low affinity pirenzepine binding sites may represent M2 receptors. These results provide further evidence for the occurrence of M2 and M3 receptors and suggest the presence of the M4 muscarinic receptor subtype in guinea-pig lung.
Haddad
E B
EB
Laboratoire de Neuroimmunopharmacologie, Université Louis Pasteur-Strasbourg I, Illkirch, France.
Trifilieff
A
A
Landry
Y
Y
Gies
J P
JP
D000818:Animals; D001667:Binding, Competitive / Q000502:physiology; D002540:Cerebral Cortex / Q000378:metabolism; D006168:Guinea Pigs; D007700:Kinetics; D008168:Lung / Q000378:metabolism*; D008297:Male; D009206:Myocardium / Q000378:metabolism; D010880:Piperidines / Q000378:metabolism*; D011817:Rabbits; D011869:Radioligand Assay; D011976:Receptors, Muscarinic / Q000378:metabolism*; D014316:Tritium
D010880:Piperidines; D011976:Receptors, Muscarinic; D014316:Tritium; C042375:4-diphenylacetoxy-1,1-dimethylpiperidinium