Characterization of neurotensin-stimulated phosphoinositide hydrolysis in brain regions of long sleep and short sleep mice.
Previous studies have shown that long sleep (LS) and short sleep (SS) mice, which were selectively bred for differences in brain sensitivity to ethanol, differ in neurotensin (NT) receptor densities in specific brain regions. The present study was designed to determine whether these receptor differences mediate differences in the effects of NT on the phosphoinositide (PI) second messenger system in four brain regions from LS and SS mice. Baseline and NT- or carbachol-stimulated PI hydrolysis were Ca(2+)-dependent. Stimulation of PI hydrolysis by NT or carbachol was region specific; NT effect was approximately equal in ventral midbrain (VMB) and entorhinal cortex (EC) with slightly less stimulation in nucleus accumbens (NA) and no effect in the cerebellum (CE). Carbachol-enhanced PI hydrolysis was greatest in the VMB followed by EC and NA with no stimulation in the CE. There were no between line (LS vs. SS) differences in carbachol effects, but stimulation by NT was greater in EC and NA from LS than from SS mice. Ethanol enhanced NT-stimulated, but not carbachol-stimulated, PI metabolism in SS and LS NA brain slices. Results with levocabastine, an inhibitor of low-affinity NT receptor (NTL) binding, suggest that NT may stimulate PI hydrolysis via NTL, as well as high-affinity receptors.
Erwin
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Alcohol Research Center, School of Pharmacy, University of Colorado Health Sciences Center, Denver 80262.
Radcliffe
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RA
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D002118:Calcium / Q000494:pharmacology; D002217:Carbachol / Q000494:pharmacology; D002531:Cerebellum / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D006634:Histamine H1 Antagonists / Q000494:pharmacology; D006868:Hydrolysis; D007294:Inositol / Q000378:metabolism; D007295:Inositol Phosphates / Q000378:metabolism*; D007700:Kinetics; D008563:Membrane Lipids / Q000096:biosynthesis / Q000378:metabolism; D008636:Mesencephalon / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008815:Mice, Inbred Strains; D009496:Neurotensin / Q000494:pharmacology*; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism; D009928:Organ Specificity; D010716:Phosphatidylinositols / Q000378:metabolism*; D010743:Phospholipids / Q000096:biosynthesis / Q000378:metabolism; D010880:Piperidines / Q000494:pharmacology; D018028:Receptors, Neurotensin / Q000235:genetics / Q000378:metabolism*; D015290:Second Messenger Systems; D012890:Sleep / Q000502:physiology*
D006634:Histamine H1 Antagonists; D007295:Inositol Phosphates; D008563:Membrane Lipids; D010716:Phosphatidylinositols; D010743:Phospholipids; D010880:Piperidines; D018028:Receptors, Neurotensin; D009496:Neurotensin; D007294:Inositol; D002217:Carbachol; C047340:levocabastine; D002118:Calcium