Nitric oxide and carbon monoxide act as inhibitory neurotransmitters in the longitudinal muscle of C57BL/6J mouse distal colon.
The present study was designed to identify the inhibitory neurotransmitters mediating nonadrenergic noncholinergic relaxation in the longitudinal muscle of C57/BL mouse distal colon. Relaxation induced by electrical field stimulation (EFS) was recorded isotonically in the presence of atropine and guanethidine. Cyclic guanosine-3',5'-monophosphate (cyclic GMP) content was measured by radioimmunoassay. EFS-induced relaxation was inhibited by nitro-L-arginine (L-NNA) and Sn (IV) protoporphyrin dichloride IX (SnPP-IX), a nitric oxide (NO) and carbon monoxide (CO) synthase inhibitor, respectively. A combination of both inhibitors produced an additive effect. ODQ, a soluble guanylate cyclase inhibitor, inhibited EFS-induced relaxation. NOR-1, a NO donor, and carbon monoxide-releasing molecule-2 (CORM-2), a CO donor, treatment relaxed the distal colon and increased cyclic GMP content. The effects of NOR-1 and CORM-2 were inhibited by ODQ. KT5823, a cyclic GMP-dependent protein kinase inhibitor, inhibited EFS-induced relaxation. EFS-induced relaxation in the presence of KT5823 was further inhibited by L-NNA, but not by SnPP-IX. In addition, KT5823 inhibited CORM-2-induced relaxation, but not NOR-1-induced relaxation. H89, a cyclic AMP-dependent protein kinase inhibitor, inhibited EFS-induced relaxation, and EFS-induced relaxation in the presence of H89 was further inhibited by L-NNA. These results suggested that NO and CO function as inhibitory neurotransmitters in the longitudinal muscle of C57BL mouse distal colon.
Hidaka
Ayako
A
Laboratory of Veterinary Pharmacology, Graduate School of Life and Environmental Science, Osaka Prefecture University, Rinku-Ourai Kita, Izumisano-shi 598-8531, Japan.
Azuma
Yasu-Taka
YT
Nakajima
Hidemitsu
H
Takeuchi
Tadayoshi
T
D000818:Animals; D001285:Atropine / Q000008:administration & dosage; D002248:Carbon Monoxide / Q000378:metabolism*; D003106:Colon / Q000378:metabolism*; D006152:Cyclic GMP / Q000378:metabolism; D004558:Electric Stimulation; D006145:Guanethidine / Q000008:administration & dosage; D006162:Guanylate Cyclase / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009126:Muscle Relaxation / Q000502:physiology; D009130:Muscle, Smooth / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*; D011863:Radioimmunoassay; D018160:Receptors, Cytoplasmic and Nuclear / Q000187:drug effects / Q000378:metabolism; D000071756:Soluble Guanylyl Cyclase
D018160:Receptors, Cytoplasmic and Nuclear; D009569:Nitric Oxide; D001285:Atropine; D002248:Carbon Monoxide; D006162:Guanylate Cyclase; D000071756:Soluble Guanylyl Cyclase; D006152:Cyclic GMP; D006145:Guanethidine