Effects of stimulation of muscarinic receptors on bladder afferent nerves in the in vitro bladder-pelvic afferent nerve preparation of the rat.
Effects of a muscarinic receptor agonist oxotremorine-M (oxo-M) on bladder afferent nerve (BAN) activity were studied in an in vitro bladder-pelvic nerve preparation. Distension of the bladder induced rhythmic bladder contractions that were accompanied by multiunit afferent firing. Intravesical administration of 25 and 50 μM oxo-M significantly increased afferent firing from 41 ± 2 spikes/s to 51 ± 4 spikes/s and 60.5 ± 5 spikes/s, respectively, but did not change the maximum amplitude of spontaneous bladder contractions. The afferent nerve firing induced by isotonic distension of the bladder (10-40 cmH(2)O) was increased 22-100% by intravesical administration of 50 μM oxo-M. Electrical stimulation on the surface of the bladder elicited action potentials (AP) in BAN. Oxo-M significantly decreased the voltage threshold by 40% (p<0.05) and increased by 157% (p<0.05) the area of the AP evoked at a submaximal stimulus intensity. These effects were blocked by intravesical injection of 5 μM atropine methyl nitrate (AMN). Intravesical administration of 5 μM AMN alone did not alter BAN firing or the amplitude of bladder contractions. The facilitatory effects induced by oxo-M on BAN activity were also suppressed (p<0.05) by intravesical administration of 2',3'-0-trinitrophenyl-ATP (TNP-ATP) (30 μM). In preparations pretreated with capsaicin (125 mg/kg, s.c.) the facilitatory effects of 50 μM oxo-M on BAN activity were absent. These results suggest that activation of muscarinic receptors facilitates mechano-sensitive, capsaicin-sensitive BAN activity in part by mechanisms involving purinergic receptors located near the luminal surface of the bladder and ATP release which presumably occurs in the urothelium.
Yu
Yongbei
Y
Department of Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, PA 15261, USA.
de Groat
William C
WC
D000200:Action Potentials / Q000187:drug effects*; D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D000283:Administration, Intravesical; D000818:Animals; D001286:Atropine Derivatives / Q000494:pharmacology; D002211:Capsaicin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation / Q000379:methods; D066298:In Vitro Techniques; D008297:Male; D018721:Muscarinic Agonists / Q000008:administration & dosage / Q000494:pharmacology*; D009119:Muscle Contraction / Q000187:drug effects*; D009475:Neurons, Afferent / Q000187:drug effects*; D010095:Oxotremorine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D010276:Parasympatholytics / Q000494:pharmacology; D058913:Purinergic Agonists / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011976:Receptors, Muscarinic / Q000378:metabolism*; D018689:Sensory System Agents / Q000494:pharmacology; D001743:Urinary Bladder / Q000187:drug effects / Q000294:innervation*
D001286:Atropine Derivatives; D018721:Muscarinic Agonists; D010276:Parasympatholytics; D058913:Purinergic Agonists; D011976:Receptors, Muscarinic; D018689:Sensory System Agents; D010095:Oxotremorine; C045674:2',3'-O-(2,4,6-trinitro-cyclohexadienylidine)adenosine 5'-triphosphate; C042743:oxotremorine M; C006649:methylatropine; D000255:Adenosine Triphosphate; D002211:Capsaicin