Coexistence of peptides with classical neurotransmitters

Hökfelt, Tomas; Millhorn, David E.; Seroogy, Kim B.; Tsuruo, Yoshihiro; Ceccatelli, Sandra; Lindh, B.; Meister, Björn; Melander, T.; Schalling, Martin; Bartfai, Tamás; Terenius, Lars

doi:10.1007/bf01945354

Cited by 313 publications

(74 citation statements)

References 126 publications

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“…The role of GAL within cholinergic neurons during the progression of Alzheimer disease remains to be elaborated. One prediction, as hypothesized by Hokfelt et al (41), suggests that as many cholinergic neurons degenerate during the disease process, the remaining cholinergic neurons may compensate by inProc. Natl.…”

Section: Methodsmentioning

confidence: 95%

Galanin antagonizes acetylcholine on a memory task in basal forebrain-lesioned rats.

Mastropaolo

Nadi

Ostrowski

et al. 1988

Proc. Natl. Acad. Sci. U.S.A.

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Galanin coexists with acetylcholine in medial septal neurons projecting to the ventral hippocampus, a projection thought to modulate memory functions. Neurochemical lesions of the nucleus basalis-medial septal area in rats impaired choice accuracy on a delayed alternation t-maze task. Acetylcholine (7.5 or 10 ,sg intraventricularly or 1 ,.g microinjected into the ventral hippocampus) significantly improved performance in the lesioned rats. Atropine (5 mg/kg intraperitoneally or 10 ,.g intraventricularly), but not mecamylamine (3 mg/kg intraperitoneally or 20 ,ug intraventricularly), blocked this action of acetylcholine, suggesting involvement of a muscarinic receptor. Galanin (100-500 ng intraventricularly or 200 ng into the ventral hippocampus) attenuated the ability of acetylcholine to reverse the deficit in working memory in the lesioned rats. The antagonistic interaction between galanin and acetylcholine suggests that endogenous galanin may inhibit cholinergic function in memory processes, particularly in pathologies such as Alzheimer disease that involve degeneration of basal forebrain neurons.Galanin (GAL) is a 29-amino acid peptide (1) localized in many regions of the mammalian central nervous system (2-5). Immunohistochemical studies revealed the coexistence of GAL and choline acetyltransferase (ChAT), the synthetic enzyme for acetylcholine (ACh), in the medial septal nucleus and nucleus basalis/diagonal band complex of primates (6, 7).In the rat, GAL coexists with ACh in the medial septal neurons projecting to the ventral hippocampus but not in the nucleus basalis neurons projecting to the cerebral cortex (8, 9). The localization of this peptide in the septo-hippocampal pathway, and the high density of GAL binding sites labeled with 1251I-labeled GAL in the ventral hippocampus (10), raise the possibility of a functional role for GAL in memory processes. To investigate the functional significance of the GAL-ACh coexistence, rats were microinjected with GAL, ACh, GAL plus ACh, or saline before behavioral testing with a t-maze delayed alternation task, in which performance was disrupted by lesions of the nucleus basalis-medial septal area (11). MATERIALS AND METHODSMale Sprague-Dawley rats, 200 g (starting weight), were housed in a temperature and humidity controlled vivarium, with lights on from 0700 to 1900. Lesions of the nucleus basalis magnocellularis (NBM) and medial septal area (MSA) were performed according to the methods of Wenk and coworkers (12). Briefly, rats were anesthetized with sodium pentobarbital (50 mg/kg, i.p.) and intracerebrally microinjected through 31-gauge hypodermic tubing with ibotenic acid (in isotonic phosphate-buffered saline, pH 7.7, shielded from light; Sigma), at five individual stereotaxic sites: 1.3 and 1.7 mm posterior to bregma, bilaterally 2.6 mm lateral to the midline, and 7.5 mm ventral to the surface of the skull with 4 ,ug in 0.4 ,ul over 2.5 min for NBM, and 0.8 mm anterior to bregma, at the midline, and 6.5 mm ventral to the surface of the skull with 6 ,u...

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Section: Methodsmentioning

confidence: 95%

Galanin antagonizes acetylcholine on a memory task in basal forebrain-lesioned rats.

Mastropaolo

Nadi

Ostrowski

et al. 1988

Proc. Natl. Acad. Sci. U.S.A.

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“…Central immunohistochemical studies show that many of the classical catecholamine neurones also store and probably release biologically active peptides as cotransmitters (Everitt et al, 1984;Hokfelt et al, 1987). Evidence for a functional role of NPY/ adrenaline or NPY/noradrenaline coexistence in neurones in cardiovascular centres of the medulla, comes from in vitro studies by Agnati et al (1983a,b) and Fuxe et al (1986;1987) who describe a reciprocal modulation of receptor number and affinity.…”

Section: Discussionmentioning

confidence: 99%

The cardiovascular actions of clonidine and neuropeptide‐Y in the ventrolateral medulla of the rat

McAuley

Macrae

Reid

1989

British J Pharmacology

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1 The cardiovascular responses to neuropeptide-Y (NPY) (25 and 50pmol) and clonidine (10 and 20nmol) were examined following microinjection into the rostral ventrolateral medulla (RVLM) and the caudal ventrolateral medulla (CVLM). Mean arterial pressure (MAP) and heart rate (HR) were measured in anaesthetized rats, pre-and post-injection. 2 The a2-adrenoceptor agonist clonidine (10 and 20nmol) reduced MAP and HR significantly when microinjected into the CVLM and RVLM. 3 NPY (25 and 50pmol) microinjected into the CVLM decreased MAP and HR. However, in the RVLM neither dose had a significant cardiovascular effect. 4 The possibility of a functional interaction between the adrenergic system and NPY was examined by co-administration of clonidine and NPY in doses that gave submaximal blood pressure responses. In the CVLM this produced hypotension and bradycardia which was similar in magnitude to the sum of their individual responses, indicating that in this area their actions appear to be independent. 5In the RVLM, where NPY has no significant cardiovascular effects, co-administration with clonidine, did not alter the response to clonidine. 6 It appears that in the areas investigated, there is no functional interaction between NPY and clonidine.

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“…They often function as messengers, and some of them coexist with and complement the classical neurotransmitters (8).…”

mentioning

confidence: 99%

Neuropeptidomics Strategies for Specific and Sensitive Identification of Endogenous Peptides

Fälth

Sköld

Svensson

et al. 2007

Molecular & Cellular Proteomics

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A new approach using targeted sequence collections has been developed for identifying endogenous peptides. This approach enables a fast, specific, and sensitive identification of endogenous peptides. Three different sequence collections were constituted in this study to mimic the peptidomic samples: SwePep precursors, SwePep peptides, and SwePep predicted. The searches for neuropeptides performed against these three sequence collections were compared with searches performed against the entire mouse proteome, which is commonly used to identify neuropeptides. These four sequence collections were searched with both Mascot and X! Tandem. Evaluation of the sequence collections was achieved using a set of manually identified and previously verified peptides. By using the three new sequence collections, which more accurately mimic the sample, 3 times as many peptides were significantly identified, with a false-positive rate below 1%, in comparison with the mouse proteome. The new sequence collections were also used to identify previously uncharacterized peptides from brain tissue; 27 previously uncharacterized peptides and potentially bioactive neuropeptides were identified. These novel peptides are cleaved from the peptide precursors at sites that are characteristic for prohormone convertases, and some of them have post-translational modifications that are characteristic for neuropeptides. The targeted protein sequence collections for different species are publicly

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Coexistence of peptides with classical neurotransmitters

Cited by 313 publications

References 126 publications

Galanin antagonizes acetylcholine on a memory task in basal forebrain-lesioned rats.

Galanin antagonizes acetylcholine on a memory task in basal forebrain-lesioned rats.

The cardiovascular actions of clonidine and neuropeptide‐Y in the ventrolateral medulla of the rat

Neuropeptidomics Strategies for Specific and Sensitive Identification of Endogenous Peptides

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