title: Neural regulation of in vitro giant contractions in the rat colon.
abstract: The rat middle colon spontaneously generates regularly occurring giant contractions (GCs) in vitro. We investigated the neurohumoral and intracellular regulation of these contractions in a standard muscle bath. cGMP content was measured in strips and single smooth muscle cells. The circular muscle strips generated spontaneous GCs. Their amplitude and frequency were significantly increased by tetrodotoxin (TTX), omega-conotoxin, N(omega)-nitro-L-arginine (L-NNA), and the dopamine D(1) receptor antagonist Sch-23390. The GCs were unaffected by hexamethonium, atropine, and antagonists of serotonergic (5-HT(1--4)), histaminergic (H(1--2)), and tachykininergic (NK(1--2)) receptors but enhanced by NK(3) receptor antagonism. The guanylate cyclase inhibitor 1H-[1,2,4]oxidiazolo[4,3-a]quinoxalin-1-one (ODQ) also enhanced GCs to the same extent as TTX and L-NNA, and each of the three agents prevented the effects of the others. GCs were abolished by electrical field stimulation, S-nitroso-N-acetyl-penicillamine, and 8-bromo-cGMP. BAY-K-8644 and apamin enhanced the GCs, but they were abolished by D-600. Basal cGMP content in strips was decreased by TTX, L-NNA, or ODQ, but these treatments had no effect on cGMP content of enzymatically dissociated single smooth muscle cells. We conclude that spontaneous contractions in the rat colonic muscle strips are not generated by cholinergic, serotonergic, or histaminergic input. Constitutive release of nitric oxide from enteric neurons sustains cGMP synthesis in the colonic smooth muscle to suppress spontaneous in vitro GCs.
authors.affiliation: Department of Surgery, Medical College of Wisconsin, Milwaukee 53266, USA.
authors.forename: A
authors.initials: A
authors.lastname: Gonzalez
authors.forename: S K
authors.initials: SK
authors.lastname: Sarna
mesh_terms: D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D001552:Benzazepines / Q000494:pharmacology; D002120:Calcium Channel Agonists / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D003106:Colon / Q000294:innervation* / Q000502:physiology*; D006152:Cyclic GMP / Q000378:metabolism; D018492:Dopamine Antagonists / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018738:Hexamethonium / Q000494:pharmacology; D007097:Imines / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology*; D009130:Muscle, Smooth / Q000294:innervation / Q000502:physiology; D018733:Nicotinic Antagonists / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism; D019335:Nitroarginine / Q000494:pharmacology; D010069:Oxadiazoles / Q000494:pharmacology; D010528:Peristalsis / Q000502:physiology*; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013498:Suramin / Q000494:pharmacology; D013779:Tetrodotoxin / Q000494:pharmacology; D020960:omega-Conotoxins / Q000494:pharmacology
chemical_list: C095284:1H-(1,2,4)oxadiazolo(4,3-a)quinoxalin-1-one; D000970:Antineoplastic Agents; D001552:Benzazepines; D002120:Calcium Channel Agonists; D002121:Calcium Channel Blockers; D018492:Dopamine Antagonists; D004791:Enzyme Inhibitors; D007097:Imines; D018733:Nicotinic Antagonists; D010069:Oxadiazoles; D011810:Quinoxalines; D020960:omega-Conotoxins; D019335:Nitroarginine; D009569:Nitric Oxide; D018738:Hexamethonium; D013779:Tetrodotoxin; D013498:Suramin; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; C014925:RMI 12330A; D006152:Cyclic GMP