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Biphasic modulation of visceral nociception by neurotensin in rat rostral ventromedial medulla.
J Pharmacol Exp Ther. 1999 Jul; 290(1):207-13.JP

Abstract

A potential role for neurotensin in the rostral ventromedial medulla (RVM) in modulation of visceral nociceptive transmission was examined in this study. Microinjection of neurotensin (3-3000 pmol) into the RVM of awake rats produced a dose-dependent inhibition of the visceromotor response (VMR) to noxious colorectal distension (CRD) that lasted 30 to 120 min. Additionally, intra-RVM injection of neurotensin (300 pmol) significantly reduced the slope of the stimulus-response function to graded CRD (20-80 mm Hg), whereas the greatest dose of neurotensin (3000 pmol) completely inhibited the VMR at all intensities of CRD. General motor function was unaffected after intra-RVM injection of neurotensin (3000 pmol). Intra-RVM injection of lesser doses of neurotensin (0.03-0.30 pmol) resulted an enhancement of the VMR to noxious CRD that had a short duration (18-30 min), and produced a leftward shift of the stimulus-response function to graded CRD without a change in the slope of the function. Additionally, intra-RVM injection of the neurotensin-receptor antagonist SR48692 (0.3-300 fmol) in naive animals produced dose-dependent inhibition of VMR to noxious CRD, whereas a lesser dose (0.03 fmol) enhanced the VMR. These data support a role for neurotensin in the RVM in biphasic modulation of visceral nociception. The results obtained with SR48692 suggest that endogenous neurotensin in the RVM modulates VMR to noxious CRD via a prominent interaction with neurotensin receptors that mediate facilitatory influences and a lesser interaction with neurotensin receptors that mediate masked inhibitory influences.

Authors+Show Affiliations

Department of Pharmacology, College of Medicine, The University of Iowa, Iowa City, Iowa, USA. murban@blue.weeg.uiowa.eduNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

10381777

Citation

Urban, M O., et al. "Biphasic Modulation of Visceral Nociception By Neurotensin in Rat Rostral Ventromedial Medulla." The Journal of Pharmacology and Experimental Therapeutics, vol. 290, no. 1, 1999, pp. 207-13.
Urban MO, Coutinho SV, Gebhart GF. Biphasic modulation of visceral nociception by neurotensin in rat rostral ventromedial medulla. J Pharmacol Exp Ther. 1999;290(1):207-13.
Urban, M. O., Coutinho, S. V., & Gebhart, G. F. (1999). Biphasic modulation of visceral nociception by neurotensin in rat rostral ventromedial medulla. The Journal of Pharmacology and Experimental Therapeutics, 290(1), 207-13.
Urban MO, Coutinho SV, Gebhart GF. Biphasic Modulation of Visceral Nociception By Neurotensin in Rat Rostral Ventromedial Medulla. J Pharmacol Exp Ther. 1999;290(1):207-13. PubMed PMID: 10381777.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Biphasic modulation of visceral nociception by neurotensin in rat rostral ventromedial medulla. AU - Urban,M O, AU - Coutinho,S V, AU - Gebhart,G F, PY - 1999/6/25/pubmed PY - 1999/6/25/medline PY - 1999/6/25/entrez SP - 207 EP - 13 JF - The Journal of pharmacology and experimental therapeutics JO - J Pharmacol Exp Ther VL - 290 IS - 1 N2 - A potential role for neurotensin in the rostral ventromedial medulla (RVM) in modulation of visceral nociceptive transmission was examined in this study. Microinjection of neurotensin (3-3000 pmol) into the RVM of awake rats produced a dose-dependent inhibition of the visceromotor response (VMR) to noxious colorectal distension (CRD) that lasted 30 to 120 min. Additionally, intra-RVM injection of neurotensin (300 pmol) significantly reduced the slope of the stimulus-response function to graded CRD (20-80 mm Hg), whereas the greatest dose of neurotensin (3000 pmol) completely inhibited the VMR at all intensities of CRD. General motor function was unaffected after intra-RVM injection of neurotensin (3000 pmol). Intra-RVM injection of lesser doses of neurotensin (0.03-0.30 pmol) resulted an enhancement of the VMR to noxious CRD that had a short duration (18-30 min), and produced a leftward shift of the stimulus-response function to graded CRD without a change in the slope of the function. Additionally, intra-RVM injection of the neurotensin-receptor antagonist SR48692 (0.3-300 fmol) in naive animals produced dose-dependent inhibition of VMR to noxious CRD, whereas a lesser dose (0.03 fmol) enhanced the VMR. These data support a role for neurotensin in the RVM in biphasic modulation of visceral nociception. The results obtained with SR48692 suggest that endogenous neurotensin in the RVM modulates VMR to noxious CRD via a prominent interaction with neurotensin receptors that mediate facilitatory influences and a lesser interaction with neurotensin receptors that mediate masked inhibitory influences. SN - 0022-3565 UR - https://www.unboundmedicine.com/medline/citation/10381777/Biphasic_modulation_of_visceral_nociception_by_neurotensin_in_rat_rostral_ventromedial_medulla_ L2 - https://jpet.aspetjournals.org/cgi/pmidlookup?view=long&pmid=10381777 DB - PRIME DP - Unbound Medicine ER -