Structure-activity studies with car☐y- and amino-terminal fragments of neurotensin on hypothalamic neurons in vitro

Baldino, Frank; Davis, Leonard G.; Wolfson, B.

doi:10.1016/0006-8993(85)91125-4

Cited by 18 publications

(6 citation statements)

References 25 publications

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“…Occurrence of calcium-independent and calcium-dependent responses of single neurones to neurotensin has been previously reported in other tissues, as in the myenteric plexus, preoptic/anterior hypothalamus and arcuate nucleus. However, in all these tissues indirect responses evoked by neurotensin were exclusively inhibitory (Williams et al 1979;Baldino et al 1985;Herbison et al 1986). The present findings in prevertebral ganglia provide original evidence for an indirect excitatory response to neurotensin.…”

Section: Discussionmentioning

confidence: 99%

“…Neurotensin has been shown to affect the excitability of single neurones in NTLIcontaining tissues such as ganglion cells in the retina (Dick & Miller, 1981), cerebral cortical neurones (Phillis & Kirkpatrick, 1980), preoptic/anterior hypothalamic (PAOH) neurones (Baldino et al 1985), neurones of the arcuate nucleus (Herbison, Hubbard & Sirett, 1986), substantia nigra (Pinnock, 1985), locus coeruleus (Young, Uhl & Kuhar, 1978), spinal cord (Suzue, Yanaihara & Otsuka, 1981;Stanzione & Zieglgansberger, 1983), and myenteric plexus (Williams, Katayama & North, 1979). No data have been reported concerning the functional role and membrane effects of this putative transmitter in prevertebral ganglia.…”

Section: Discussionmentioning

confidence: 99%

“…Membrane responses to the C-terminal fragment neurotensin8 13 Biological activity of neurotensin1-13 has been attributed to the C-terminal portion of the molecule since biological responses similar to those caused by neurotensin1-13 were observed when the C-terminal hexapeptide fragment neurotensin8-13 was used (Carraway & Leeman, 1975;Pinnock, 1985;Baldino, Davis & Wolfson, 1985).…”

Section: Transient Responsesmentioning

confidence: 99%

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The electrophysiological effects of neurotensin on neurones of guinea‐pig prevertebral sympathetic ganglia.

Stapelfeldt

Szurszewski

1989

The Journal of Physiology

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SUMMARY1. The membrane effects of neurotensin on neurones of guinea-pig prevertebral ganglia were investigated by means of intracellular recording techniques in vitro.2. Neurotensin (2-5 ,UM) applied by superfusion caused depolarizing responses in fifty-seven of seventy-four neurones tested in the inferior mesenteric ganglion and thirty-seven of forty-seven neurones tested in the coeliac plexus. The remaining neurones tested showed no membrane response.3. Responses to neurotensin could be discriminated into two different types of membrane depolarizations on the basis of their different time courses and pharmacological characteristics: a steady-state type of depolarization and a transient type of depolarization. Seven of fifty-seven responsive neurones tested in the inferior mesenteric ganglion and ten of thirty-seven responsive neurones tested in the coeliac plexus responded to neurotensin with a depolarization which was maintained constant as long as neurotensin was superfused over the preparation (steady-state type). Forty-eight of fifty-seven responsive neurones tested in the inferior mesenteric ganglion and twenty of thirty-seven responsive neurones tested in the coeliac plexus responded with a transient depolarization which was followed by a repolarization in the maintained presence of neurotensin (transient type). A combination of both types of responses was observed in two neurones tested in the inferior mesenteric ganglion and in seven neurones tested in the coeliac plexus.4. Steady-state type responses were characterized by a slowly developing membrane depolarization which reached a plateau and lasted throughout the presence of neurotensin. Amplitude and time course of this response were not altered in a solution containing hexamethonium (10 ram) and atropine (10 tM) or by a solution low in calcium (1 mM) and high in magnesium (15 mM).5. Transient type depolarizations evoked by neurotensin were faster in reaching their maximum and were followed by a repolarization during the maintained presence of neurotensin. Responses similar in time course and amplitude were obtained in solutions containing hexamethonium (10-100 /tM) and atropine (10 /IM).However, transient responses were abolished in a solution low in calcium (1 mM) and high in magnesium (15 mM) and were markedly attenuated in ganglia treated with capsaicin (3 /tM). 7. Both types of depolarizations were observed when the C-terminal hexapeptide fragment neurotensin 8-13 was used.8. It was concluded that neurotensin caused an increase in excitability in a large portion of prevertebral sympathetic neurones of guinea-pigs by interaction with receptors specific for the C-terminal, bioactive portion of the molecule. The response of the large majority of neurones was mediated through Ca2+-dependent release of a non-cholinergic excitatory transmitter from capsaicin-sensitive nerve terminals.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Transient Responsesmentioning

confidence: 99%

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The electrophysiological effects of neurotensin on neurones of guinea‐pig prevertebral sympathetic ganglia.

Stapelfeldt

Szurszewski

1989

The Journal of Physiology

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“…The possibility of a degradation fragment formed before the internalization being transported to the substantia nigra must be excluded, because enzymatic cleavage of iodinated neurotensin probably occurs from the carboxy terminal end, thus removing the latter end of the amino acid chain and consequently eliminating the ability of the radioactive fi-agments to bind to neurotensin receptors (Checler et al, 1985). Indeed, in vivo and in vitro studies have now clearly demonstrated that the last six amino acids of the neurotensin carboxy terminal are essential for the binding of this peptide to its receptors (Rivier et al, 1977;Baldino et al, 1985;Kitabgi et al, 1980). Therefore, one may assume that the degradation fragment detected in the substantia nigra cannot be formed before the internalization process in the striaturn, because internalization and subsequent transport would not be possible.…”

Section: Resultsmentioning

confidence: 99%

Identification of Intact Neurotensin in the Substantia Nigra After Its Retrograde Axonal Transport in Dopaminergic Neurons

Castel

Faucher

Cuine

et al. 1991

Journal of Neurochemistry

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Two hours after the injection of (3-[125I]iodotyrosyl3) neurotensin into the striatum, a labeling was observed in the ipsilateral substantia nigra. In the present study, we demonstrated by HPLC that this radioactivity corresponded to intact neurotensin and to degradation products of this peptide. This finding provides the first clearcut evidence that a neuropeptide can be internalized and retrogradely transported in brain neurons. Therefore, the fact that intact neurotensin can be seen to exist over a long period of time in the cell body suggests that the retrograde transport process could perhaps be involved in the long-term effects of neuropeptides.

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“…3). Except that the half-maximal concentration (EC50) of NT for mRNA-induced receptors (92 nM) was 6-40 times higher than those reported for native receptors Rioux, Quirion, Regoli, Leblanc & St-Pierre, 1980;Checler, Labbe, Granier, Van Rietschoten, Kitabgi & Vincent, 1982), the pharmacological properties of mRNA-induced NT receptors were essentially the same as those of native NT receptors found in smooth muscles (Carraway & Leeman, 1975;Checler et al 1982), brains (Nemeroff, Luttinger & Prange, 1980;Baldino, Davis & Wolfson, 1985), and neuronal cells (Amar, Mazella, Checler, Kitabgi & Vincent, 1985). The C-terminal hexapeptide of NT was the minimal sequence that could fully activate NT receptors, whereas the N-terminal octapeptide was ineffective either as an agonist (Fig.…”

Section: Identification Of Receptorsmentioning

confidence: 89%

Neurotensin and acetylcholine evoke common responses in frog oocytes injected with rat brain messenger ribonucleic acid.

Hirono¹,

Ito²,

Sugiyama³

1987

The Journal of Physiology

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SUMMARY1. The intracellular reaction mechanism underlying electrophysiological responses evoked by neurotensin (NT) was studied using Xenopus laevis oocytes injected with poly (A)+ messenger ribonucleic acid (mRNA) isolated from rat brains.2. A few days after the injection of mRNA, oocytes were found to acquire sensitivity to NT and substance P.3. Under voltage-clamp conditions (-60 mV), application of NT to mRNAinjected oocytes produced transient and oscillatory inward currents which began after a delay of several tens of seconds. These inward currents were accompanied by an increase in membrane conductance.4. NT receptors on mRNA-injected oocytes showed essentially the same pharmacological properties as those of native NT receptors.5. The NT response showed desensitization and was not readily recovered even after extensive washing of cells for more than 30 min.6. NT response was suppressed when the muscarinic acetylcholine (ACh) response of the same cell, which was also induced by the same mRNA, was desensitized by a large dose of ACh.7. NT response and ACh response showed many similarities: they were both inhibited by pertussis toxin and intracellular ethyleneglycol-bis-(f-aminoethylether)

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Structure-activity studies with car☐y- and amino-terminal fragments of neurotensin on hypothalamic neurons in vitro

Cited by 18 publications

References 25 publications

The electrophysiological effects of neurotensin on neurones of guinea‐pig prevertebral sympathetic ganglia.

The electrophysiological effects of neurotensin on neurones of guinea‐pig prevertebral sympathetic ganglia.

Identification of Intact Neurotensin in the Substantia Nigra After Its Retrograde Axonal Transport in Dopaminergic Neurons

Neurotensin and acetylcholine evoke common responses in frog oocytes injected with rat brain messenger ribonucleic acid.

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