Radioligand binding characteristics of the chicken cardiac muscarinic receptor.
The muscarinic receptor present in chicken cardiac membranes was characterised using a ligand binding approach and compared to the M1, M2 and M3 receptors that can be identified in ligand binding studies at present. [3H]N-methylscopolamine and [3H]pirenzepine appeared to label the same population of muscarinic receptors in chicken cardiac membranes since the density of sites labeled by the two radioligands was similar. Furthermore, affinity estimates of 8 muscarinic receptor antagonists for chicken cardiac muscarinic receptors were the same irrespective of whether [3H]N-methylscopolamine or [3H]pirenzepine was used as the radioligand. The chicken cardiac muscarinic receptor displayed high affinity for pirenzepine (pKi = 7.9) and so did not appear to represent an M2 receptor. Despite the high affinity of chicken cardiac muscarinic receptors for pirenzepine, affinity estimates for dicyclomine (pKi = 8.0), CPPS (pKi = 8.4) and 4DAMP (pKi = 8.6) in chicken heart were not consistent with the presence of M1 receptors. The chicken cardiac muscarinic receptor also displayed significant differences to the M3 receptor since it displayed high affinity for AF-DX 116 (pKi = 7.1) and methoctramine (pKi = 8.4). Finally, chicken heart muscarinic receptors displayed high affinity for gallamine (pKi = 7.0) and pirenzepine suggesting that the receptor was different to the M4 muscarinic receptor of the NG108-15 cell line. These findings suggest that chicken heart expresses a novel muscarinic receptor subtype distinct from the M1, M2, M3, and M4 subtypes already described.
Michel
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Institute of Pharmacology, Syntex Research, Palo Alto, CA 94303.
Whiting
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D000818:Animals; D001667:Binding, Competitive / Q000187:drug effects; D002460:Cell Line; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D002645:Chickens; D066298:In Vitro Techniques; D007700:Kinetics; D009206:Myocardium / Q000378:metabolism*; D019832:N-Methylscopolamine; D010276:Parasympatholytics / Q000378:metabolism; D010890:Pirenzepine / Q000494:pharmacology; D011869:Radioligand Assay; D051381:Rats; D011976:Receptors, Muscarinic / Q000378:metabolism*; D012602:Scopolamine Derivatives / Q000494:pharmacology; D013363:Submandibular Gland / Q000187:drug effects / Q000378:metabolism
D010276:Parasympatholytics; D011976:Receptors, Muscarinic; D012602:Scopolamine Derivatives; D010890:Pirenzepine; D019832:N-Methylscopolamine