Differential inhibitory control of circular and longitudinal smooth muscle layers of Balb/C mouse small intestine.
We examined the inhibitory mediators acting on each of the longitudinal (LM) and circular muscle (CM) layers of mouse small intestine in the presence of atropine, prazosin and timolol. Nitric oxide (NO) and apamin-sensitive mediators exerted an inhibitory tone on pacing frequency in CM, observed as an increased frequency upon treatment with N-omega-nitro-l-arginine (LNNA) or apamin. This effect was not seen in LM. 1H-(1,2,4)oxadiazolo(4,3-A)quinazoline-1-one (ODQ) abolished the relaxation in response to electric field stimulation (EFS) in LM in a manner similar to LNNA indicating that the inhibitory mediator in this layer in NO acting via soluble guanylate cyclase. On the other hand, in CM neither LNNA nor apamin was capable of reducing the inhibition in response to EFS and their combination left a residual relaxation of 25%. ODQ reduced the EFS-evoked relaxation more effectively than LNNA at higher frequencies indicating that another ODQ-sensitive mediator was active in CM. ODQ also blocked the relaxation to exogenous vasoactive intestinal peptide in CM. In LM, the relaxation due to sodium nitroprusside was equally blocked by ODQ and apamin, while in CM, its effects were only reduced by ODQ and not apamin. These results indicate that there are differences in the inhibitory mediators and the mechanisms of action involved in LM and CM relaxation.
El-Yazbi
Ahmed F
AF
Department of Pharmacology, 9-10 Medical Sciences Building, University of Alberta, Edmonton, Canada AB T6G 2H7.
Schulz
Richard
R
Daniel
Edwin E
EE
D000818:Animals; D001030:Apamin / Q000494:pharmacology; D006152:Cyclic GMP / Q000031:analogs & derivatives / Q000494:pharmacology; D004307:Dose-Response Relationship, Radiation; D004347:Drug Interactions; D004558:Electric Stimulation / Q000379:methods; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005071:Evoked Potentials / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D066298:In Vitro Techniques; D007421:Intestine, Small / Q000294:innervation* / Q000502:physiology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D009126:Muscle Relaxation / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D009130:Muscle, Smooth / Q000187:drug effects / Q000294:innervation / Q000502:physiology*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D019335:Nitroarginine / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology; D010069:Oxadiazoles / Q000494:pharmacology
C116907:1H-(1,2,4)oxadiazolo(4,3-a)-quiloxalin-1-one; D004791:Enzyme Inhibitors; D020030:Nitric Oxide Donors; D010069:Oxadiazoles; D009599:Nitroprusside; D019335:Nitroarginine; D001030:Apamin; C016276:8-bromocyclic GMP; D006152:Cyclic GMP