Potentiation of nerve-induced bladder responses by tetraethylammonium in relation to junctional and extrajunctional muscarinic receptors.

1 The single stimulus responses elicited in the rat urinary bladder were enhanced up to 3 fold by tetraethylammonium chloride (TEA) in the range 2.5 to 10 mM. Responses elicited by repetitive stimulation at 20 Hz were potentiated much less by 2.5 and 5 mM TEA; 10 mM TEA depressed the responses to less than control levels.2 The responses elicited in preparations treated with tetrodotoxin or botulinum toxin during the 20 Hz stimulus trains were one third to one half of control, while single stimulus responses were abolished altogether. After 10 mM TEA the response to the 20 Hz stimulus trains were near control but the single stimulus responses were not restored at all.3 The single stimulus response of control and of TEA-treated bladder preparations were unaffected by atropine (2 x 10(-6) M) but responses elicited by a 20 Hz stimulus train were reduced more than 40% by atropine. After 5 mM TEA the responses to the 20 Hz stimulus trains that had been partially blocked by atropine were immediately restored to near control levels.4 The responses of bladders to carbachol were dose-dependent in the range 10(-6) to 10(-5) M and were atropine-sensitive. After 5 mM TEA the means of the responses produced by graded doses of carbachol were less than control; muscarinic receptors that were blocked by TEA are probably also atropine-sensitive.5 It is suggested that muscarinic receptors in the rat urinary bladder may be divided into: (1) junctional receptors that are resistant to atropine and may be indirectly affected by TEA and (2) extrajunctional receptors that are blocked by atropine and may be directly affected by TEA.