Evidence for additional neurotensin receptor subtypes: neurotensin analogs that distinguish between neurotensin-mediated hypothermia and antinociception

Tyler, Beth M.; Cusack, Bernadette; Douglas, Christopher L.; Souder, Terrance; Richelson, Elliott

doi:10.1016/s0006-8993(98)00150-4

Cited by 36 publications

(25 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These experiments were performed to demonstrate that the hypothermic effect of NT69L was independent of ischemia and isoflurane anesthesia, both of which have been associated with spontaneous hypothermia. 22,23 The changes in brain temperature in the current study closely paralleled the core hypothermic response reported by Tyler et al, when a hypothermic selective neurotensin analog (NT27) was administered directly into the brain, 24 providing further support that NT69L can directly modulate brain temperature, even after ischemia.…”

Section: Discussionsupporting

confidence: 87%

Untitled

2001

Academic Emergency Medicine

View full text Add to dashboard Cite

Abstract. Objective: To determine whether the neurotensin analog NT69L, administered systemically, could induce mild brain hypothermia after asphyxial cardiac arrest (ACA) in rats. Methods: The study design was experimental, blinded, randomized, and approved by the animal use committee. All rats had continuous monitoring of brain temperature and sustained 8 minutes of ACA, resuscitation, and either saline or NT69L intravenously after return of spontaneous circulation (ROSC). Rats surviving 14 days after ACA had a neurological deficit score (NDS) and a Morris Water Maze (MWM) test. Results: Seven of eight rats in each group survived 14 days. Brain temperature was less than 35ЊC 13.1 Ϯ 3 minutes (meanϮ standard deviation) after NT69L vs controls that remained 37.5ЊC at the same ambient temperature (p < 0.05 ANOVA). The NT69L group remained below 35ЊC for 300 Ϯ 100 minutes while the controls remained at 37.5 Ϯ 0.5ЊC. The NDS in the NT69L rats was 3 Ϯ 3% vs controls 26 Ϯ 8% (p < 0.05, Kruskal-Wallis, 0% = normal, 100% = brain dead). The NT69L rats performed better on the MWM vs the controls (22 Ϯ 8 sec vs 45 Ϯ 26 sec, respectively, p < 0.05 ANOVA). Conclusions: NT69L induced rapid and prolonged mild brain hypothermia after ACA in this rat model and reduced neurological deficits.

show abstract

Section: Discussionsupporting

confidence: 87%

Untitled

2001

Academic Emergency Medicine

View full text Add to dashboard Cite

show abstract

“…SR 48692 is a NT receptor antagonist that is relatively selective for NT 1 , the receptor subtype that has so far been implicated in the pre-and postsynaptic effects of NT on the mesolimbic and nigrostriatal dopamine system (Gully et al, 1993;Tyler et al, 1998;Vincent et al, 1999). NT 2 , another Gprotein coupled NT receptor, is also widely expressed in the brain including dopaminergic nuclei (the ventral tegmental area and substantia nigra) and the NAcc and its activation could be involved in APD-induced Fos expression in some brain regions (Walker et al, 1998).…”

Section: Discussionmentioning

confidence: 99%

Neurotensin Receptor Antagonist SR 142948A Alters Fos Expression and Extrapyramidal Side Effect Profile of Typical and Atypical Antipsychotic Drugs

Binder

Kinkead

Owens

et al. 2004

Neuropsychopharmacol

View full text Add to dashboard Cite

Antipsychotic drugs (APDs) have previously been shown to alter Fos expression in a regionally specific manner. Increases in Fos expression in the nucleus accumbens (NAcc) are common to all clinically effective APDs. In contrast, APD-induced Fos expression increases in the caudate-putamen (CPu) and prefrontal cortex (PFC) are associated with the extrapyramidal side effect liability of typical APDs or the effectiveness against negative symptoms of atypical APDs, respectively. Considerable evidence suggests that the neuropeptide neurotensin (NT) mediates some of the effects of APDs. To determine whether NT neurotransmission is also involved in APD-induced Fos expression in brain regions relevant for therapeutic efficacy, the NT receptor antagonist SR 142948A (10 or 100 mg/ kg i.p.) was coadministered with APDs (haloperidol (2.0 mg/kg s.c.), olanzapine (5 mg/kg i.p.), or clozapine (20 mg/kg s.c.)). Fos expression was evaluated in the PFC, NAcc shell, dorsomedial, and dorsolateral CPu and the lateral septum. SR 142948A attenuated haloperidolinduced Fos expression in the CPu but, in contrast, increased olanzapine-induced Fos expression in this brain region. The effects of the NT receptor antagonist were paralleled by its effects on catalepsy in olanzapineFbut not haloperidolFtreated animals.

show abstract

“…An alternative mechanism for the increased potency is transport to the site of action facilitated by the glycan. Additionally, the glycosylated peptide may act with high affinity on an as yet undefined neurotensin receptor subtype (36) or may be a selective high affinity ligand for a particular state of a neurotensin receptor subtype. Yet another possibility is that the relevant targeted neurotensin receptors may be closely co-localized with carbohydrate binding sites and that the glycan may serve as an "address label," a mechanism postulated for certain opiate peptides.…”

Section: Discussionmentioning

confidence: 99%

Contulakin-G, an O-Glycosylated Invertebrate Neurotensin

Craig¹,

Norberg²,

Griffin³

et al. 1999

Journal of Biological Chemistry

Self Cite

179

168

View full text Add to dashboard Cite

We have purified contulakin-G, a 16-amino acid Olinked glycopeptide (pGlu-Ser-Glu-Glu-Gly-Gly-SerAsn-Ala-Thr-Lys-Lys-Pro-Tyr-Ile-Leu-OH, pGlu is pyroglutamate) from Conus geographus venom. The major glycosylated form of contulakin-G was found to incorporate the disaccharide ␤-D-Galp-(133)-␣-D-GalpNAc-(13) attached to Thr 10 . The C-terminal sequence of contulakin-G shows a high degree of similarity to the neurotensin family of peptides. Synthetic peptide replicates of Gal(␤33) GalNAc(␣3)Thr 10 contulakin-G and its nonglycosylated analog were prepared using an Fmoc (9-fluorenylmethoxycarbonyl) protected solid phase synthesis strategy. The synthetic glycosylated contulakin-G, when administered intracerebroventricular into mice, was found to result in motor control-associated dysfunction observed for the native peptide. Contulakín-G was found to be active at 10-fold lower doses than the nonglycosylated Thr 10 contulakin-G analog. The binding affinities of contulakin-G and the nonglycosylated Thr 10 contulakin-G for a number of neurotensin receptor types including the human neurotensin type 1 receptor (hNTR1), the rat neurotensin type 1 and type 2 receptors, and the mouse neurotensin type 3 receptor were determined. The binding affinity of the nonglycosylated Thr 10 contulakin-G was approximately an order of magnitude lower than that of neurotensin [1][2][3][4][5][6][7][8][9][10][11][12][13] for all the receptor types tested. In contrast, the glycosylated form of contulakin-G exhibited significantly weaker binding affinity for all of the receptors tested. However, both contulakin-G and nonglycosylated Thr 10 contulakin-G were found to be potent agonists of rat neurotensin receptor type 1. Based on these results, we conclude that O-linked glycosylation appears to be a highly unusual strategy for increasing the efficacy of toxins directed against neurotransmitter receptors.

show abstract

Evidence for additional neurotensin receptor subtypes: neurotensin analogs that distinguish between neurotensin-mediated hypothermia and antinociception

Cited by 36 publications

References 24 publications

Untitled

Untitled

Neurotensin Receptor Antagonist SR 142948A Alters Fos Expression and Extrapyramidal Side Effect Profile of Typical and Atypical Antipsychotic Drugs

Contulakin-G, an O-Glycosylated Invertebrate Neurotensin

Contact Info

Product

Resources

About