Mode and mechanism of neurotensin action in rat proximal colon.
This study examined the mechanism of action of neurotensin on intraluminal pressure in rat proximal colon. The direct and indirect contractile response to neurotensin (100 nM) was abolished in Ca(2+)-free solution, and was antagonized by nifedipine (1-5-10 nM) and potentiated by Bay K 8644 (methyl 1,4-dihydro-2,6-dimethyl-3-nitro-4-(2-trifluoromethylphenyl)- pyridine-5-carboxylate) (10-100-1000 nM). Neurotensin, in the presence of nifedipine (10 nM) and atropine (1 microM), induced a tetrodotoxin-insensitive inhibitory effect, which was antagonized by SR 48692 (2[(1-(7-chloro-4-quinolinyl)-5-(2,6-dimethoxy-phenyl)pyrazol-3-yl) carbonyl amino]tricyclo (3.3.1.1.(3.7)) decan-2-carboxylic acid) (300 nM) or apamin (0.1 microM). The results demonstrate that the neurotensin response is dependent on the influx of Ca2+ via L-type channels and results from summation of excitatory and inhibitory effects.
Mulè
F
F
Dipartimento di Biologia Cellulare e dello Sviluppo, Università di Palermo, Italy.
Serio
R
R
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000818:Animals; D001030:Apamin / Q000494:pharmacology; D001285:Atropine / Q000494:pharmacology; D018723:Bethanechol / Q000494:pharmacology; D002118:Calcium / Q000502:physiology; D002120:Calcium Channel Agonists / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D018679:Cholinergic Agonists / Q000494:pharmacology; D018680:Cholinergic Antagonists / Q000494:pharmacology; D003106:Colon / Q000187:drug effects*; D066298:In Vitro Techniques; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects*; D009496:Neurotensin / Q000494:pharmacology*; D009543:Nifedipine / Q000494:pharmacology; D011720:Pyrazoles / Q000494:pharmacology; D011804:Quinolines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D018028:Receptors, Neurotensin / Q000037:antagonists & inhibitors
D002120:Calcium Channel Agonists; D002121:Calcium Channel Blockers; D018679:Cholinergic Agonists; D018680:Cholinergic Antagonists; D011720:Pyrazoles; D011804:Quinolines; D018028:Receptors, Neurotensin; D018723:Bethanechol; C079087:SR 48692; D001030:Apamin; D009496:Neurotensin; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D001285:Atropine; D009543:Nifedipine; D002118:Calcium