M-15: high-affinity chimeric peptide that blocks the neuronal actions of galanin in the hippocampus, locus coeruleus, and spinal cord.

Bartfai, Tamás; Bedecs, Katarina; Land, Tiit; Langel, Ülo; Bertorelli, Rosalia; Girotti, Prisca; Consolo, S.; Xu, Xiao‐Jun; Wiesenfeld‐Hallin, Zsuzsanna; Nilsson, Stefan

doi:10.1073/pnas.88.23.10961

Cited by 134 publications

(77 citation statements)

References 22 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…As shown in Table I, both GALR1 and GALR2 receptors bound the full-length peptide porcine galanin-(1-29) with high affinity, as well as the truncated analogs galanin-(1-16) and galanin-(1-15). Both receptor subtypes also displayed high affinity for the putative galanin antagonists M15, M35, M40, and C7 (15,29,34,35), all of which share a common galanin-(1-13) N terminus. Furthermore, binding affinity was lost for either receptor subtype when the first two N-terminal residues were deleted, as in the case of galanin- .…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Expression Cloning of a Rat Hypothalamic Galanin Receptor Coupled to Phosphoinositide Turnover

Smith

Forray

Walker

et al. 1997

Journal of Biological Chemistry

189

200

View full text Add to dashboard Cite

The neuropeptide galanin is widely distributed throughout the central and peripheral nervous systems and participates in the regulation of processes such as nociception, cognition, feeding behavior, and insulin secretion. Multiple galanin receptors are predicted to underlie its physiological effects. We now report the isolation by expression cloning of a rat galanin receptor cDNA distinct from GALR1. The receptor, termed GALR2, was isolated from a rat hypothalamus cDNA library using a 125 I-porcine galanin (

show abstract

Section: Resultsmentioning

confidence: 99%

“…Multiple receptor subtypes are proposed to underlie the physiological effects of galanin (15)(16)(17)(18), but until recently only one cloned galanin receptor subtype (GALR1) had been described (19 -21). We report here the isolation by expression cloning and the pharmacological characterization of a novel galanin receptor from a rat hypothalamic cDNA library.…”

mentioning

confidence: 99%

Expression Cloning of a Rat Hypothalamic Galanin Receptor Coupled to Phosphoinositide Turnover

Smith

Forray

Walker

et al. 1997

Journal of Biological Chemistry

189

200

View full text Add to dashboard Cite

show abstract

“…In contrast to these inhibitory actions, exogenous galanin has no effect on the increased release of ACh that occurs when a rodent is exposed to a novel environment (9). Neither of the galanin antagonists has an effect on ACh release or on cognition in the absence of exogenously administered galanin (5,6). Similarly, whereas exogenous galanin inhibits long-term potentiation (LTP) in hippocampal CA1 slices that is reversed by the M40 galanin antagonist, M40 has no effect on LTP when applied alone (10).…”

mentioning

confidence: 99%

“…These findings have led to a number of functional studies addressing the role played by galanin in the basal forebrain cholinergic system, including its effects on acetylcholine (ACh) release as well as learning and memory. Acute administration of galanin into the hippocampus or third ventricle of rodents inhibits scopolamineinduced ACh release in a dose-dependent manner and is reversed by the coadministration of the chimeric-peptide galanin receptor antagonists M15 and M40 (5,6). Centrally administered galanin also has inhibitory effects on several tests of learning and memory (7,8).…”

mentioning

confidence: 99%

Galanin regulates the postnatal survival of a subset of basal forebrain cholinergic neurons

O’Meara

Coumis

Yang

et al. 2000

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

120

View full text Add to dashboard Cite

The neuropeptide galanin colocalizes with choline acetyltransferase, the synthetic enzyme for acetylcholine, in a subset of cholinergic neurons in the basal forebrain of rodents. Chronic intracerebroventricular infusion of nerve growth factor induces a 3-to 4-fold increase in galanin gene expression in these neurons. Here we report the loss of a third of cholinergic neurons in the medial septum and vertical limb diagonal band of the basal forebrain of adult mice carrying a targeted loss-of-function mutation in the galanin gene. These deficits are associated with a 2-fold increase in the number of apoptotic cells in the forebrain at postnatal day seven. This loss is associated with marked agedependent deficits in stimulated acetylcholine release, performance in the Morris water maze, and induction of long-term potentiation in the CA1 region of the hippocampus. These data provide unexpected evidence that galanin plays a trophic role to regulate the development and function of a subset of septohippocampal cholinergic neurons.T he 29 amino acid peptide galanin (1) colocalizes with choline acetyltransferase (ChAT) in 30-35% of cholinergic neurons in the medial septum and vertical limb diagonal band (VLDB) of the basal forebrain in the rat (2, 3). Most, if not all, of these galaninpositive cholinergic neurons project to the hippocampus (2, 4). These findings have led to a number of functional studies addressing the role played by galanin in the basal forebrain cholinergic system, including its effects on acetylcholine (ACh) release as well as learning and memory. Acute administration of galanin into the hippocampus or third ventricle of rodents inhibits scopolamineinduced ACh release in a dose-dependent manner and is reversed by the coadministration of the chimeric-peptide galanin receptor antagonists M15 and M40 (5, 6). Centrally administered galanin also has inhibitory effects on several tests of learning and memory (7,8). In contrast to these inhibitory actions, exogenous galanin has no effect on the increased release of ACh that occurs when a rodent is exposed to a novel environment (9). Neither of the galanin antagonists has an effect on ACh release or on cognition in the absence of exogenously administered galanin (5, 6). Similarly, whereas exogenous galanin inhibits long-term potentiation (LTP) in hippocampal CA1 slices that is reversed by the M40 galanin antagonist, M40 has no effect on LTP when applied alone (10). In addition, there is increasing evidence that the M15 and M40 ligands may act as partial agonists in the hippocampus (11, 12) and as full agonists in vitro to the cloned galanin receptor subtypes (13). These somewhat conflicting data emphasize the limitations of the pharmacological tools that are currently available and cast some doubt on the role played by endogenously secreted galanin in the modulation of steady-state ACh release.We have recently generated mice carrying a loss-of-function mutation in the galanin gene (14) and have demonstrated that galanin is (i) essential for the developmental s...

show abstract

“…Galanin hyperpolarizes noradrenergic cell bodies in the locus coeruleus (11) and inhibits the release of glutamate, but not of raminobutyric acid, in the hippocampus (12). This fragmentary list of the effects of exogenously applied galanin explains much of the interest in this neuropeptide in psychopharmacology, in endocrinology, in prevention of anoxic damage (13), and in management of chronic pain and explains the interest in galanin antagonists as possible therapeutic agents in Alzheimer disease (14,15 (17) and by receptor autoradiography (18,19) in the central nervous system (CNS) and in the periphery. It was shown that actions mediated by galanin receptors involve pertussis toxin-ADP-ribosylable G proteins of inhibitory (Gi) or regulatory (Go) type (20)(21)(22).…”

mentioning

confidence: 99%

Galanin-receptor ligand M40 peptide distinguishes between putative galanin-receptor subtypes.

Bartfai

Langel

Bedecs

et al. 1993

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

Self Cite

123

View full text Add to dashboard Cite

The glanin-receptor Hlgand M40 [galanin-(1-12)-Pro3-(Ala-Leu)2-AIa amide] binds with high affinity to galanin-binding sites in hippocampal, hypothalamic, and spinal cord membranes and in membranes from Rin m5F rat insulinoma cells . Receptor autoradlographic studies show that M40 (1 "M) displaces galanin from binding sites in the hippocampus, hypothalamus, and spinal cord. In the brain, M40 acts as a potent galanin-receptor antagonist: M40, in doses comparable to that of galanin, antagonizes the stimulatory effects of glanin on feeding, and it blocks the galaninergic inhibition of the scopolamine-induced acetylcholne release in the ventral hippocampus in vivo. In contrast, M40 completely fails to antagonize both the galanin-mediated inhibition of the glucoseinduced insulin release in isolated mouse pancreatic islets and the inhibitory effects of galanin on the forskolin-stimulated accumulation of 3',5'-cAMP in Rin mSF cells; instead M40 is a weak agonist at the galanin receptors in these two systems. M40 acts as a weak antagonist of galanin in the spinal flexor reflex model. These results suggest that at least two subtypes of the glanin receptor may exist. Hypothalamic and hippocampal galanin receptors represent a putative central galaninreceptor subtpe (GL-1-receptor) that is blocked by M40. The pancreatic galanin receptor may represent another subtype (GL-2-receptor) that recognizes M40, but as a weak agonist. The galanin receptors in the spinal cord occupy an intermediate position between these two putative subtypes.Galanin is an important neuroendocrine peptide with multiple biological and pharmacological actions (1). It is a potent inhibitor of glucose-induced insulin release (2), it inhibits hippocampal acetylcholine release (3) induced by systemic administration of scopolamine (4), it impairs cognitive performance (5, 6), it stimulates feeding behavior upon hypothalamic or intracerebroventricular injection (7,8), it stimulates growth hormone secretion (9), and it has a biphasic effect on the spinal flexor reflex (10). Galanin hyperpolarizes noradrenergic cell bodies in the locus coeruleus (11) Accordingly, a galanin-receptor subtype has been suggested, which is composed of nervous tissue and pancreatic galanin receptors that recognize the N-terminal 1-to 15-aa or 1-to 16-aa fragment of galanin as high-affinity agonists, whereas another putative galanin-receptor subtype in smooth muscle requires both the N and C terminus of galanin for binding and biological action (25). On the basis of the differential affinity ofgalanin (3-29) and ofa galanin-receptor antagonist M15 (17), existence of an additional galaninreceptor subtype has been suggested in the rat anterior pituitary (26), which differs from other CNS galanin receptors. Finally, galanin-(1-15)-binding sites have been demonstrated in the dorsal hippocampus, neocortex, and neostriatum, areas that seem to lack galanin-(1-29)-binding sites (27).

show abstract

M-15: high-affinity chimeric peptide that blocks the neuronal actions of galanin in the hippocampus, locus coeruleus, and spinal cord.

Abstract: The 20

Cited by 134 publications

References 22 publications

Expression Cloning of a Rat Hypothalamic Galanin Receptor Coupled to Phosphoinositide Turnover

Expression Cloning of a Rat Hypothalamic Galanin Receptor Coupled to Phosphoinositide Turnover

Galanin regulates the postnatal survival of a subset of basal forebrain cholinergic neurons

Galanin-receptor ligand M40 peptide distinguishes between putative galanin-receptor subtypes.

Contact Info

Product

Resources

About