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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 
 
 
 
 

Selectivity of partial agonists related to oxotremorine based on differences in muscarinic receptor reserve between the guinea pig ileum and urinary bladder.

The muscarinic effects of analogs of oxotremorine were compared on strips of the guinea pig ileum and urinary bladder. In a series of eight analogs, full or nearly full contractile responses compared to carbachol were observed on the ileum. On the bladder, the analogs were full agonists, partial agonists, or competitive antagonists. Although EC50 values estimated on the bladder were 10- to 20-fold greater than those obtained on the ileum, the dissociation constant and relative efficacy of each agonist were similar in the two tissues, as were dissociation constants of competitive antagonists including pirenzepine. The ability to discriminate between responses in the ileum and bladder was related to intrinsic efficacy. Highly efficacious compounds such as carbachol and oxotremorine-M were full agonists in both tissues, although less potent on the bladder. Compounds having intermediate intrinsic efficacy, e.g., oxotremorine, were partial agonists on the bladder, whereas BM 5, having low intrinsic efficacy, was a competitive antagonist. These results suggest a mechanism, based on tissue differences in receptor reserve, by which selectivity may be achieved among muscarinic stimulants, even in the absence of distinct subtypes of muscarinic receptors.[1]

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