Muscarinic receptor subtype specificity of 5'-(isobutylthio)-adenosine (SIBA) and its analogs.
1. 5'(Isobutylthio)-adenosine (SIBA) and its analogs, at 100 microM, inhibited [3H]N-methyl-scopolamine binding to homogenates of whole brain and cortex (mainly M1 subtype receptors) by 11-30% and to cerebellum (mainly M2 subtype receptors) by 20-39%. 2. At 0.01-1.0 microM, stimulation of [3H]QNB and NMS-inaccessible [3H]QNB binding was observed, with the most induced by 1 microM 3-deaza-SIBA. 3. In contrast, [3H]pirenzepine ([3H]PZ) binding to whole brain and cortex was inhibited in a dose-dependent manner with Ki values in the microM range. 4. As antagonists of acetylcholine-induced contraction of guinea pig ileum (mainly M2 subtype receptors), the analogs were slightly more potent than pirenzepine, but several orders of magnitude less than atropine; the order of potency was opposite that determined for the binding of [3H]PZ to cortex. 5. Thus, SIBA and its analogs may have differential effects on muscarinic receptor subtypes and show some specificity for the M1 receptor subtype.
Smejkal
R M
RM
Division of Biochemistry, Walter Reed Army Institute of Research, Washington, DC 20307-5100.
Abalis
I
I
Pankaskie
M C
MC
Chiang
P K
PK
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D000970:Antineoplastic Agents / Q000378:metabolism*; D001923:Brain Chemistry / Q000187:drug effects; D055598:Chemical Phenomena; D002621:Chemistry; D003839:Deoxyadenosines / Q000031:analogs & derivatives* / Q000378:metabolism; D006168:Guinea Pigs; D007082:Ileum / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D010890:Pirenzepine / Q000494:pharmacology; D011813:Quinuclidinyl Benzilate / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D011976:Receptors, Muscarinic / Q000187:drug effects*; D013872:Thionucleosides / Q000378:metabolism*
D000970:Antineoplastic Agents; D003839:Deoxyadenosines; D011976:Receptors, Muscarinic; D013872:Thionucleosides; C013919:5'-deoxy-5'-S-isobutylthioadenosine; D010890:Pirenzepine; D011813:Quinuclidinyl Benzilate; D000109:Acetylcholine