title: The role of M2 muscarinic receptor subtypes mediating contraction of the circular and longitudinal smooth muscle of the pig proximal urethra.
abstract: OBJECTIVE
  We investigated the characterization of muscarinic receptor subtypes in the female pig urethra.
  
  
  METHODS
  The affinities of muscarinic antagonists against carbachol responses were calculated in normal and cyclic adenosine monophosphate (cAMP) elevated tissues (contraction with KCl and relaxation with isoprenaline) using longitudinal and transverse strips of urethra.
  
  
  RESULTS
  In displacement experiments with 1-quinuclidinyl [phenyl-4-3H] benzilate inhibitory constant (pKi) values of 4-diphenylacetoxyl-N-methyl-piperidine methiodide (DAMP) M3 selective antagonist) and methoctramine (M2 antagonist) indicated the presence of the M2 receptor. In functional studies contraction responses to carbachol were greater in longitudinal than in circular muscle. After cAMP elevation the contraction response increased in circular muscles to the level close to that of longitudinal muscles but did not change significantly in cAMP elevated longitudinal muscle. On normal circular tissues 4-DAMP had high mean affinity (mean apparent pKB value 9.3) but with a Schild slope of less than unity (0.76). Methoctramine competitively antagonized carbachol responses (mean affinity [pA2] value 6.9). On normal longitudinal tissues 4-DAMP and methoctramine competitively antagonized carbachol responses (mean pA2 9.0 and 6.2, respectively). After cAMP elevation in circular tissues mean pA2 values for 4-DAMP (8.7) were significantly lower (p = 0.0015), and those for methoctramine (7.3) were significantly higher (p = 0.0193) than in normal tissues. In longitudinal tissues the mean pA2 value for methoctramine (6.9) was significantly greater than in normal tissues (p <0.0001) but the value for 4-DAMP (8.8) did not alter.
  
  
  CONCLUSIONS
  Pig urethra appears to have predominantly M2 muscarinic receptors. Contraction of the normal urethra appears to be predominantly mediated by M2 and M3 receptors in circular muscle but by M3 receptors in longitudinal muscle. After cAMP elevation a contribution to contraction of M2 receptors appeared to be demonstrated in the 2 tissues but the involvement of M2 receptors appeared greater in circular muscle.
authors.affiliation: Department of Biomedical Science, University of Sheffield, United Kingdom.
authors.forename: Tomonori
authors.initials: T
authors.lastname: Yamanishi
authors.forename: Christopher R
authors.initials: CR
authors.lastname: Chapple
authors.forename: Kosaku
authors.initials: K
authors.lastname: Yasuda
authors.forename: Ken-Ichiro
authors.initials: K
authors.lastname: Yoshida
authors.forename: Russell
authors.initials: R
authors.lastname: Chess-Williams
mesh_terms: D000818:Animals; D046508:Culture Techniques; D005260:Female; D009119:Muscle Contraction / Q000502:physiology*; D009130:Muscle, Smooth / Q000502:physiology*; D043585:Receptor, Muscarinic M2; D043587:Receptor, Muscarinic M3; D011976:Receptors, Muscarinic / Q000502:physiology*; D013552:Swine; D014521:Urethra / Q000502:physiology*; D014563:Urodynamics / Q000502:physiology
chemical_list: D043585:Receptor, Muscarinic M2; D043587:Receptor, Muscarinic M3; D011976:Receptors, Muscarinic