Antagonism by SR 48692 of mechanical responses to neurotensin in rat intestine

Mulè, F; Serio, Rosa; Postorino, A.; Vetri, T.; Bonvissuto, F.

doi:10.1111/j.1476-5381.1996.tb15216.x

Cited by 20 publications

(6 citation statements)

References 21 publications

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“…Its action on intestinal smooth muscle is complex and has not been fully investigated. In vitro , NT elicits contractions but also relaxation of rat colonic preparations depending on the experimental conditions ( Mulé & Serio, 1997 ); it acts either directly on smooth muscle or indirectly through the neuronal release of acetylcholine and substance P ( Mulé et al ., 1996 ).…”

Section: Introductionmentioning

confidence: 99%

In vitro functional evidence of different neurotensin‐receptors modulating the motor response of human colonic muscle strips

Croci

Aureggi

Guagnini

et al. 1999

British J Pharmacology

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1 The newly developed non-peptide neurotensin (NT)-receptor antagonists SR 48692 and SR 142948 were used to challenge NT responses of human colonic circular smooth muscle strips in vitro. The presence of NT 1 and NT 2 receptor transcripts in this tissue was tested by reverse transcriptase polymerase chain reaction (RT ± PCR) analysis. 2 NT potently and dose-dependently contracted muscle strips, with signi®cant regional di erences in potency and e cacy between the transverse and distal colon: EC 50 , 3.6 and 7.5 nM; the maximal e ect was 70 and 55% of 0.1 mM carbachol. Colonic responses to NT in both segments were virtually the same in the presence of atropine (1 mM), levocabastine (10 mM) or tetrodotoxin (1 mM). 3 SR 142948 (10 nM ± 1 mM) competitively antagonized NT responses in the transverse and distal colon with similar a nities: pA 2 values 8.71 and 8.45, slopes 0.98 and 0.99. SR 48692 (10 nM ± 10 mM) antagonized the NT response competitively in the distal colon (pA 2 6.55, slope 0.79) and non-competitively in the transverse colon (pA 2 8.0, slope 0.51). Neither compound had any agonist e ect. 4 The fact that the speci®c antagonists prevented NT-evoked atropine-and tetrodotoxin-insensitive mechanical responses of colonic muscle strips is highly consistent with the presence in these tissues of non-neuronal NT receptors, whose heterogeneity in the transverse segment is supported by the non-competitive antagonism of SR 48692. The ®nding of NT 1 receptor transcript in both transverse and distal colon suggests its identity with the lower a nity site disclosed functionally by SR 48692 in these segments.

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Section: Introductionmentioning

confidence: 99%

In vitro functional evidence of different neurotensin‐receptors modulating the motor response of human colonic muscle strips

Croci

Aureggi

Guagnini

et al. 1999

British J Pharmacology

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“…Aside from the bladder and kidneys, labeled peptide shows moderately high uptake values in the HT‐29 tumor with NT positive receptor and organs such as intestine, stomach, and lung, which could be the main target organs. As the neuromodulatory activity of NT at the periphery level are well founded, and due to the evidence that has been found of NT receptor expression in the intestine, a considerable uptake in the gastrointestinal tract can be assumed.…”

Section: Resultsmentioning

confidence: 99%

A^99mTc-tricine-HYNIC-labeled peptide targeting the neurotensin receptor for single-photon imaging in malignant tumors

Erfani

Ahrabi

Shafiei

et al. 2014

J. Label Compd. Radiopharm

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In this study, a new neurotensin (NT) analog was labeled with (99m) Tc via HYNIC chelator and tricine as coligand and investigated further. An NT (7-13) analog was prepared, and labeling with (99m) Tc was performed. The internalization rate and biodistribution of radiopeptide were studied in HT-29 cells and nude mice bearing tumor, respectively. Radiolabeling with (99m) Tc was performed at high specific activities (54 MBq/nmol) with an acceptable labeling yield (>95%). In vitro cell line studies showed a specific internalization uptake up to 13.23 ± 0.45% during 4 h which was blocked in the presence of excess cold peptide to 0.83 ± 0.15%. In biodistribution studies, uptake was observed in NT receptor-positive organs so that after 1 h the uptakes in mouse intestine and tumor were 1.23 ± 0.16% ID/g and 1.12 ± 0.11% ID/g, respectively. In animals co-injected with excess cold peptide, reduction uptake in tumor and intestines were 73% (1.10% vs. 0.29% ID/g at 4 h) and 61% (1.22% vs. 0.47% ID/g at 4 h) respectively. Predominant renal excretion pathway with a highest accumulation of activity in bladder was observed for this radiopeptide. This radiolabeled peptide could be a candidate for detection of NT positive tumors.

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“…In the intestinal smooth muscle, SR48692 acts as a selective antagonist against NT in both the contracting effect, brought about via ACh release from cholinergic nerves, and relaxant effect via direct action on smooth muscle cells to activate apamin-sensitive K + channels [22,23]. Its potency is distinctly higher for the latter than the former effect of NT (in the rat, [23]; in the guinea-pig, Unno, T., Doi, T., Komori, S. and Ohashi, H., unpublished data). Taken together, it seems reasonable to assume that at least three subtypes of NT receptor exist in the intestine, which can be classified by SR48692.…”

Section: Discussionmentioning

confidence: 99%

“…48692 inhibits the NT-induced contraction and relaxation with significantly-different potencies [23]. These observations suggest the possible existence of distinct NT receptor subtypes.…”

mentioning

confidence: 83%

“…SR 48692 antagonizes the action of NT to facilitate high K + evoked dopamine release in brain slices [11]. It selectively inhibits the contraction and relaxation of the intestinal smooth muscle [22,23] and the modulation of peristaltic activity in intestinal segments [25], induced by NT. However, SR 48692 fails to affect NT-induced hypothermia and analgesia [5].…”

Section: Methodsmentioning

confidence: 99%

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Potentiatin by Neurotensin of Carbachol-Induced Tension Development in .BETA.-Escin-Skinned Smooth Muscle of Guinea-Pig Ileum.

Unno

Shingu

Isogai

et al. 1998

The Journal of Veterinary Medical Science

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ABSTRACT. Effect of neurotensin (NT) on carbachol(CCh)-induced tension development due to Ca 2+ release from intracellular stores was investigated in β-escin-skinned smooth muscle of guinea-pig ileum. NT (10 nM) increased the tension development in response to CCh. NT also increased the tension response to caffeine, another stored-Ca 2+ releaser. NT did not exert such an effect in pertusis toxin (PTX)-treated preparations. Treatment with isoprenaline to elevate endogenous cyclic AMP levels or with dibutyryl cyclic AMP did not affect the effect of NT. A nonpeptide NT antagonist, SR 48692, failed to block the effect of NT. NT shifted the pCa-tension relationship in the lower direction of Ca 2+ concentration. NT was incapable of releasing Ca 2+ from intracellular stores. The results suggest that NT may cause an increase in Ca 2+ sensitivity of contractile elements to potentiate the CCh-induced tension development due to release of stored Ca 2+ and that the effect is mediated by SR 48692-insensitive NT receptors linked to a PTX-sensitive G protein which works with no relation to a change in cytosolic cyclic AMP levels. -KEY WORDS: calcium release, carbachol, GTP-binding protein, intestinal smooth muscle, neurotensin.J. Vet. Med. Sci. 60(11): 1227-1232, 1998 48692 inhibits the NT-induced contraction and relaxation with significantly-different potencies [23]. These observations suggest the possible existence of distinct NT receptor subtypes.In some cellular models including mouse neuroblastoma N1E115 cells, evidence has been provided that NT receptors couple to G proteins and that the receptor activation causes mobilization of intracellular Ca 2+ , stimulation of inositol phosphates and of cyclic GMP formation, and inhibition of cyclic AMP formation [1,4,9,11,27]. All the NT receptormediated events in cellular models are reported to be blocked by SR 48692 [11,27].In the present study, the effect of NT on tension responses to carbachol (CCh) (acting at muscarinic receptors) mediated by Ca 2+ release from intracellular stores was investigated in β-escin-skinned smooth muscle of guinea-pig ileum, in an attempt to explore the possible modulation by NT of muscarinic tension responses in the intestinal smooth muscle. MATERIALS AND METHODSMuscle strips (5 mm long, 0.3 mm wide) were dissected from the longitudinal muscle layer of the ileum of male guinea-pigs (350-450 g). The muscle strip was mounted horizontally in a 0.3-ml organ bath, with one end of the strip fixed to the rubber bottom of the bath with a pin and the other end attached to the thin lever of an isometric force transducer (TB-612T; Nihon Kohden, Tokyo), as described elsewhere [8]. The organ bath was filled with a physiological salt solution (PSS, composition given below) kept at 23°C, and the muscle strip was equilibrated for 30-60 min under a tension of 150-180 mg. The muscle strip * CORRESPONDENCE TO: KOMORI, S., Laboratory of Pharmacology, Department of Veterinary Medicine, Faculty of Agriculture, Gifu University, 1-1 Yanagido, Gifu 501-1193, Japan.Neuroten...

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Antagonism by SR 48692 of mechanical responses to neurotensin in rat intestine

Cited by 20 publications

References 21 publications

In vitro functional evidence of different neurotensin‐receptors modulating the motor response of human colonic muscle strips

In vitro functional evidence of different neurotensin‐receptors modulating the motor response of human colonic muscle strips

A^99mTc-tricine-HYNIC-labeled peptide targeting the neurotensin receptor for single-photon imaging in malignant tumors

Potentiatin by Neurotensin of Carbachol-Induced Tension Development in .BETA.-Escin-Skinned Smooth Muscle of Guinea-Pig Ileum.

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Antagonism by SR 48692 of mechanical responses to neurotensin in rat intestine

Cited by 20 publications

References 21 publications

In vitro functional evidence of different neurotensin‐receptors modulating the motor response of human colonic muscle strips

In vitro functional evidence of different neurotensin‐receptors modulating the motor response of human colonic muscle strips

A99mTc-tricine-HYNIC-labeled peptide targeting the neurotensin receptor for single-photon imaging in malignant tumors

Potentiatin by Neurotensin of Carbachol-Induced Tension Development in .BETA.-Escin-Skinned Smooth Muscle of Guinea-Pig Ileum.

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Product

Resources

About

A^99mTc-tricine-HYNIC-labeled peptide targeting the neurotensin receptor for single-photon imaging in malignant tumors