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Mediators of nonadrenergic, noncholinergic inhibition in the proximal, middle and distal regions of rat colon.
Br J Pharmacol. 1993 Feb; 108(2):348-55.BJ

Abstract

1. The mediators of non-adrenergic non-cholinergic (NANC) relaxation of the longitudinal muscle of rat proximal, middle and distal colon were examined in vitro. 2. Electrical transmural stimulation (TMS) of proximal, middle and distal segments of rat colon induced NANC relaxations which were inhibited by tetrodotoxin (1 microM), but not by atropine (1 microM) or guanethidine (4 microM). 3. In the proximal colon, L-nitro-arginine (N5-nitroamidino-L-2,5-diaminopentanoic acid) inhibited the TMS-induced NANC relaxation and L-arginine (1 mM) reversed this inhibition. Nitric oxide (0.3-10 microM) induced relaxation of the proximal segment. 4. NANC relaxation of the proximal segments was still evident after desensitization to vasoactive intestinal peptide (VIP). A VIP antagonist (VIP 10-28, 10 microM) had no effect on the TMS-induced NANC relaxation, which was also resistant to alpha-chymotrypsin (2 units ml-1) and a substance P antagonist ([D-Pro2, D-Trp7,9]substance P, 1 microM). 5. In the middle colon, L-nitro-arginine did not inhibit the TMS-induced NANC relaxation in 6 of 9 preparations tested and partially inhibited the relaxation in the other 3 preparations. L-Arginine did not reverse the partial inhibition. 6. Complete desensitization to VIP was not achieved in the middle colon. The VIP antagonist had no effect on the TMS-induced NANC relaxation. After alpha-chymotrypsin treatment of the segment, desensitization of the segments to substance P, or in the presence of the substance P antagonist, the TMS-induced NANC relaxation was augmented. 7. In the distal colon, L-nitro-arginine did not have any significant effect on the TMS-induced relaxation and nitric oxide did not induce relaxation. The VIP antagonist significantly inhibited TMS-induced NANC relaxation. Alpa-Chymotrypsin-treatment of the distal segments resulted in significant inhibition of NANC relaxation. No desensitization to substance P was achieved. Treatment with the substance P antagonist had no effect. 8. These results suggest that nitric oxide is the mediator of the NANC inhibitory response in the proximal region of rat colon; in the middle colon, substance P acts as an excitatory neurotransmitter, antagonizing the NANC relaxation caused by the mediator of the response, which is still uncertain. Our results suggest that that VIP is the most likely candidate as a NANC transmitter in the distal colon.

Authors+Show Affiliations

Department of Veterinary Pharmacology, College of Agriculture, University of Osaka Prefecture, Sakai, Japan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

7680592

Citation

Suthamnatpong, N, et al. "Mediators of Nonadrenergic, Noncholinergic Inhibition in the Proximal, Middle and Distal Regions of Rat Colon." British Journal of Pharmacology, vol. 108, no. 2, 1993, pp. 348-55.
Suthamnatpong N, Hata F, Kanada A, et al. Mediators of nonadrenergic, noncholinergic inhibition in the proximal, middle and distal regions of rat colon. Br J Pharmacol. 1993;108(2):348-55.
Suthamnatpong, N., Hata, F., Kanada, A., Takeuchi, T., & Yagasaki, O. (1993). Mediators of nonadrenergic, noncholinergic inhibition in the proximal, middle and distal regions of rat colon. British Journal of Pharmacology, 108(2), 348-55.
Suthamnatpong N, et al. Mediators of Nonadrenergic, Noncholinergic Inhibition in the Proximal, Middle and Distal Regions of Rat Colon. Br J Pharmacol. 1993;108(2):348-55. PubMed PMID: 7680592.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Mediators of nonadrenergic, noncholinergic inhibition in the proximal, middle and distal regions of rat colon. AU - Suthamnatpong,N, AU - Hata,F, AU - Kanada,A, AU - Takeuchi,T, AU - Yagasaki,O, PY - 1993/2/1/pubmed PY - 1993/2/1/medline PY - 1993/2/1/entrez SP - 348 EP - 55 JF - British journal of pharmacology JO - Br J Pharmacol VL - 108 IS - 2 N2 - 1. The mediators of non-adrenergic non-cholinergic (NANC) relaxation of the longitudinal muscle of rat proximal, middle and distal colon were examined in vitro. 2. Electrical transmural stimulation (TMS) of proximal, middle and distal segments of rat colon induced NANC relaxations which were inhibited by tetrodotoxin (1 microM), but not by atropine (1 microM) or guanethidine (4 microM). 3. In the proximal colon, L-nitro-arginine (N5-nitroamidino-L-2,5-diaminopentanoic acid) inhibited the TMS-induced NANC relaxation and L-arginine (1 mM) reversed this inhibition. Nitric oxide (0.3-10 microM) induced relaxation of the proximal segment. 4. NANC relaxation of the proximal segments was still evident after desensitization to vasoactive intestinal peptide (VIP). A VIP antagonist (VIP 10-28, 10 microM) had no effect on the TMS-induced NANC relaxation, which was also resistant to alpha-chymotrypsin (2 units ml-1) and a substance P antagonist ([D-Pro2, D-Trp7,9]substance P, 1 microM). 5. In the middle colon, L-nitro-arginine did not inhibit the TMS-induced NANC relaxation in 6 of 9 preparations tested and partially inhibited the relaxation in the other 3 preparations. L-Arginine did not reverse the partial inhibition. 6. Complete desensitization to VIP was not achieved in the middle colon. The VIP antagonist had no effect on the TMS-induced NANC relaxation. After alpha-chymotrypsin treatment of the segment, desensitization of the segments to substance P, or in the presence of the substance P antagonist, the TMS-induced NANC relaxation was augmented. 7. In the distal colon, L-nitro-arginine did not have any significant effect on the TMS-induced relaxation and nitric oxide did not induce relaxation. The VIP antagonist significantly inhibited TMS-induced NANC relaxation. Alpa-Chymotrypsin-treatment of the distal segments resulted in significant inhibition of NANC relaxation. No desensitization to substance P was achieved. Treatment with the substance P antagonist had no effect. 8. These results suggest that nitric oxide is the mediator of the NANC inhibitory response in the proximal region of rat colon; in the middle colon, substance P acts as an excitatory neurotransmitter, antagonizing the NANC relaxation caused by the mediator of the response, which is still uncertain. Our results suggest that that VIP is the most likely candidate as a NANC transmitter in the distal colon. SN - 0007-1188 UR - https://www.unboundmedicine.com/medline/citation/7680592/Mediators_of_nonadrenergic_noncholinergic_inhibition_in_the_proximal_middle_and_distal_regions_of_rat_colon_ L2 - https://onlinelibrary.wiley.com/resolve/openurl?genre=article&sid=nlm:pubmed&issn=0007-1188&date=1993&volume=108&issue=2&spage=348 DB - PRIME DP - Unbound Medicine ER -