Atropine resistance and muscarinic receptors in the rat urinary bladder

The action of an anticholinesterase and an antimuscarinic drug upon nerve-induced contractions of the rat urinary bladder were examined during transmural stimulation at 20 Hz. Responses were graded in magnitude by limiting the duration of the stimulus trains. 2 Responses of low magnitude produced by short stimulus trains were unchanged by atropine; however, maximal responses resulting from long stimulus trains were diminished in magnitude and shortened in duration. 3 Responses of small magnitude elicited by short stimulus trains involve muscarinic receptors in close proximity to the neuroeffector junction and are resistant to atropine. 4 Maximal responses elicited by long stimulus trains involve 'junctional' muscarinic receptors as well as receptors located at the periphery of the junction; the 'extrajunctional' receptors are blocked by atropine. 5 Responses of low magnitude produced by short stimulus trains were unaffected by echothiophate; however, the duration of maximal responses resulting from the long stimulus trains was extended. 6 The inhibition of cholinesterase did not increase the occupation of muscarinic receptors by the transmitter; however, after large quantities of transmitter were released by the long stimulus trains the association between the receptors and acetylcholine was prolonged.