Characterization of muscarinic receptor subtypes in human tissues.
The affinities of selective, pirenzepine and AF-DX 116, and classical, N-methylscopolamine and atropine, muscarinic cholinergic receptor antagonists were investigated in displacement binding experiments with [3H]Pirenzepine and [3H]N-methylscopolamine in membranes from human autoptic tissues (forebrain, cerebellum, atria, ventricle and submaxillary salivary glands). Affinity estimates of N-methylscopolamine and atropine indicated a non-selective profile. Pirenzepine showed differentiation between the M1 neuronal receptor of the forebrain and the receptors in other tissues while AF-DX 116 clearly discriminated between muscarinic receptors of heart and glands. The results in human tissues confirm the previously described selectivity profiles of pirenzepine and AF-DX 116 in rat tissues. These findings thus reveal the presence also in man of three distinct muscarinic receptor subtypes: the neuronal M1, the cardiac M2 and the glandular M3.
Giraldo
E
E
Department of Biochemistry, Istituto De Angeli S.p.A., Milan, Italy.
Martos
F
F
Gomez
A
A
Garcia
A
A
Vigano
M A
MA
Ladinsky
H
H
Sanchez de La Cuesta
F
F
D001921:Brain / Q000378:metabolism*; D002531:Cerebellum / Q000378:metabolism; D006325:Heart Atria / Q000378:metabolism; D006352:Heart Ventricles / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D009206:Myocardium / Q000378:metabolism*; D019832:N-Methylscopolamine; D009928:Organ Specificity; D010890:Pirenzepine / Q000378:metabolism*; D011976:Receptors, Muscarinic / Q000378:metabolism*; D012602:Scopolamine Derivatives / Q000378:metabolism*; D013363:Submandibular Gland / Q000378:metabolism*
D011976:Receptors, Muscarinic; D012602:Scopolamine Derivatives; D010890:Pirenzepine; D019832:N-Methylscopolamine