Effects of selective cholinergic antagonists and alpha,beta-methylene ATP on guinea-pig urinary bladder contractions in vivo following pelvic nerve stimulation.
1. An in vivo preparation measuring functional detrusor muscle strength in terms of intravesical bladder pressure (Pves) following in situ pelvic nerve stimulation has been developed in urethane-anaesthetized guinea pigs. 2. The increase in bladder pressure following pelvic nerve stimulation was abolished by topical lidocaine or tetrodotoxin, suggesting a neurogenic origin for the in vivo contractile response. 3. Cholinergic antagonists (i.v.) decreased the amplitude of the peak pressure response by about 50% at both high (30 Hz) and low (5 Hz) stimulation rates, with a rank order of potency of atropine greater than propantheline greater than oxybutynin greater than hexahydrosiladifenidol greater than pirenzepine greater than methoctramine. 4. The P2 purine receptor antagonist, alpha,beta-methylene ATP (i.v.), antagonized pelvic nerve-stimulated bladder contractions differentially at 5 and 30 Hz. At low frequencies, alpha, beta-methylene ATP was both more potent (2.5-fold) and more efficacious (-77 compared to -55% delta) than at 30 Hz. Atropine and alpha,beta-methylene ATP together completely inhibited the contractile response. 5. Together, the findings indicate that in guinea pigs, urinary bladder contractions induced by pelvic nerve stimulation in vivo may be mediated by both muscarinic and purinergic receptors and that these bladder contractions may be mediated by the M2 beta subtype rather than by M1 or M2 alpha muscarinic receptors.
Peterson
J S
JS
Nova Pharmaceutical Corporation, Baltimore, Maryland 21224-2788.
Noronha-Blob
L
L
D000255:Adenosine Triphosphate / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D004558:Electric Stimulation; D005260:Female; D006168:Guinea Pigs; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D010276:Parasympatholytics / Q000494:pharmacology*; D010388:Pelvis / Q000294:innervation*; D001743:Urinary Bladder / Q000187:drug effects* / Q000294:innervation
D010276:Parasympatholytics; D001285:Atropine; D000255:Adenosine Triphosphate; C002630:alpha,beta-methyleneadenosine 5'-triphosphate