1. Structure-antinociceptive activity of neurotensin and some novel analogues in the periaqueductal gray region of the brainstem.
- Author
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al-Rodhan NR, Richelson E, Gilbert JA, McCormick DJ, Kanba KS, Pfenning MA, Nelson A, Larson EW, and Yaksh TL
- Subjects
- Animals, Brain Stem drug effects, Cyclic GMP biosynthesis, Female, Humans, In Vitro Techniques, Microinjections, Neuroblastoma metabolism, Periaqueductal Gray drug effects, Rats, Rats, Inbred Strains, Reaction Time drug effects, Receptors, Neurotensin, Receptors, Neurotransmitter metabolism, Structure-Activity Relationship, Tumor Cells, Cultured drug effects, Tumor Cells, Cultured metabolism, Analgesics pharmacology, Brain Stem metabolism, Neurotensin analogs & derivatives, Neurotensin pharmacology, Periaqueductal Gray metabolism
- Abstract
Neurotensin, an endogenous tridecapeptide, produces a potent, naloxone-insensitive antinociceptive response when it is microinjected into the periaqueductal gray region of the rat brainstem. In the present study, the ED50 for neurotensin in inducing antinociception was 1.5 nmol, two times more potent than morphine. We sought to find whether neurotensin's antinociceptive effects were mediated by the same receptor that mediates its other functions. We found that the structure-activity relationship of neurotensin-induced antinociception was different from that required for the stimulation of intracellular cyclic GMP production in neuroblastoma clone N1E-115 and the binding to N1E-115 cells, human brain tissue, or rat periaqueductal gray. These data suggest there exists a subtype of neurotensin receptors in neural tissue that mediates its antinociceptive actions.
- Published
- 1991
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