Human galanin: Primary structure and indentification of two molecular forms

Bersani, Maurizio; Johnsen, Anders H.; Højrup, Peter; Dunning, Beth E.; Andreasen, Jan Jesper; Holst, Jens J.

doi:10.1016/0014-5793(91)80585-q

Cited by 117 publications

(61 citation statements)

References 18 publications

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“…The COOH-terminal aa of turtle galanin contained Thr, Gly, Lys, and Arg at positions 29, 30, 31, and 32, respectively, indicating the possible COOH-terminal amidation of the turtle galanin at Thr. This notion is consistent with reports on birds (27) and rodents (25,26) but inconsistent with those published on primates (5,13,14). It has been demonstrated that the NH 2 -terminal portion of galanin, particularly the first 15 aa, has been conserved across vertebrate species and is important for receptor interaction and galanin bioactivity in various tissues.…”

Section: Resultssupporting

confidence: 68%

“…The PCR product was run using 1.5% (wt/vol) agarose gel electrophoresis with 40 mM Tris-acetate buffer (pH 8.0) containing 1 mM EDTA and visualized with the use of ethidium bromide (0.5 g/ml). Gene-specific oligonucleotide primers for amplification of turtle galanin cDNAs were designed on the basis of the conserved regions of human (5,14), chicken (27), quail (27), rat (25), and mouse (26) galanin. Accordingly, the forward and reverse primers for the 3Ј-RACE system were 5Ј-CCACATGCAGTA-GAGATAACCAC-3Ј and 5Ј-CTAATACGACTCACTATAGGGC-AAGCAGTGGTATCAACGCAGAGT-3Ј (the so-called universal primer mix A by SMART RACE kit), respectively.…”

Section: Methodsmentioning

confidence: 99%

“…In mice and humans, the galanin gene contains six exons and five introns (14,26), and its mRNA consists of 398 -989 base pairs (bp), depending on the species (5, 8, 13, 14, 25-27, 35, 41, 42, 50). The open-reading frame encodes a mouse (124 aa) (26) and human (125 aa) (5,14) preprogalanin protein. In vertebrates, mature galanin derived from the preprogalanin COOH terminus contains 29 aa and amidates with glycine at the final residue (threonine or alanine) (2, 5, 8, 13, 14, 18, 25-27, 35, 41, 42, 50, 52, 56 -59).…”

mentioning

confidence: 99%

“…In vertebrates, mature galanin derived from the preprogalanin COOH terminus contains 29 aa and amidates with glycine at the final residue (threonine or alanine) (2, 5, 8, 13, 14, 18, 25-27, 35, 41, 42, 50, 52, 56 -59). However, macaque and human galanins have 30 aa and lack COOH-terminal amidation (5,13), and there is also a second form of human galanin consisting of the first 19 NH 2 -terminal aa residues (5). These observations suggest that there are species-specific isoforms and lengths of galanin.…”

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confidence: 99%

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A preprogalanin cDNA from the turtle pituitary and regulation of its gene expression

Yu¹,

Pon²,

Ku³

et al. 2007

American Journal of Physiology-Regulatory, Integrative and Comp

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Galanin is a hormone 29 or 30 amino acids (aa) long that is widely distributed within the body and exerts numerous biological effects in vertebrates. To fully understand its physiological roles in reptiles, we analyzed preprogalanin cDNA structure and expression in the turtle pituitary. Using the Chinese soft-shell turtle (Pelodiscus sinensis order Testudines), we obtained a 672-base pair (bp) cDNA containing a 99-bp 5Ј-untranslated region, a 324-bp preprogalanin coding region, and a 249-bp 3Ј-untranslated region. The open-reading frame encoded a 108-aa preprogalanin protein with a putative 23-aa signal sequence at the NH 2 terminus. Based on the location of putative Lys-Arg dibasic cleavage sites and an amidation signal of Gly-Lys-Arg, we propose that turtle preprogalanin is processed to yield a 29-aa galanin peptide with Gly 1 and Thr 29 substitutions and a COOH-terminal amidation. Sequence comparison revealed that turtle preprogalanin and galanin-29 had 48 -81% and 76 -96% aa identities with those of other vertebrates, respectively, suggesting their conservative nature. Expression of the turtle galanin gene was detected in the pituitary, brain, hypothalamus, stomach, liver, pancreas, testes, ovaries, and intestines, but not in the adipose or muscle tissues, suggesting tissue-dependent differences. An in vitro study that used pituitary tissue culture indicated that treatment with 17␤-estradiol, testosterone, or gonadotropin-releasing hormone resulted in increased galanin mRNA expression with dose-or time-dependent differences, whereas leptin and neuropeptide Y reduced galanin mRNA levels. These results suggest a hormone-dependent effect on hypophyseal galanin mRNA expression.estrogen; androgen; gonadotropin-releasing hormone; neuropeptide Y; leptin GALANIN, a 29-amino acid (aa) hormone, was first isolated from porcine intestine and used to stimulate contractions of rat smooth muscle and to cause hyperglycemia in dogs (52). Since its discovery, galanin has also been found to exhibit numerous actions in vertebrates. For example, it induces feeding and the release of pituitary hormones [i.e., luteinizing hormone (LH) and growth hormone (GH)], decreases circulating levels of oxytocin, plays an antinociceptive role in the spinal cord, is involved in gastrointestinal motility and autonomic function, inhibits memory and learning, and promotes smooth muscle contractions (12). Moreover, clinical investigations have shown that galanin levels and galanin receptors are related to human disorders, such as Alzheimer disease and obesity (12). In reptiles, galanin can control gastrointestinal blood flow (24) and female oviposition (29). Although its mechanism of action in these reptilian physiological processes remains unknown, galanin in mammals reportedly operates via G i /G 0 -proteincoupled receptors involving effector systems such as K ϩ channels, Ca 2ϩ channels, and adenylate cyclase (3). In mice and humans, the galanin gene contains six exons and five introns (14, 26), and its mRNA consists of 398 -989 base pairs (bp),...

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Section: Resultssupporting

confidence: 68%

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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A preprogalanin cDNA from the turtle pituitary and regulation of its gene expression

Yu¹,

Pon²,

Ku³

et al. 2007

American Journal of Physiology-Regulatory, Integrative and Comp

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“…Galanin is found throughout the central and peripheral nervous systems and the gastrointestinal tract (1)(2)(3)(4). The effects of this peptide include inhibition of insulin release (5-7), inhibition of neurotransmiters involved in regulation and memory acquisition (8), modulation of food intake (9, 10) and sexual behavior (11), as well as effects on controlling pain threshold (12,13) and in the pathogenesis of Alzheimer's disease (14).…”

mentioning

confidence: 99%

Synthesis of galmic: A nonpeptide galanin receptor agonist

Ceide

Trembleau²,

Haberhauer³

et al. 2004

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

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Galanin is a neuropeptide with a wide variety of biological functions. Few nonpeptide ligands, capable of activating galanin receptors, are available today. Based on known pharmacophores of galanin and the tripeptidomimetic galnon, a combinatorial library was formulated, synthesized, and screened against the galanin receptor. An active compound, galmic, was identified and tested in vitro and in vivo for its affinity and efficacy at galanin receptors. The present work describes the total synthesis of galmic, the synthesis of its oxazole precursors, the coupling of the building blocks into a linear trimer, and the macrolactamization reaction.galnon ͉ mimetic G alanin is a 29-aa-long (30 aa in humans) neuroendocrine peptide, whose physiological functions are regulated by G protein-coupled receptors. Galanin is found throughout the central and peripheral nervous systems and the gastrointestinal tract (1-4). The effects of this peptide include inhibition of insulin release (5-7), inhibition of neurotransmiters involved in regulation and memory acquisition (8), modulation of food intake (9, 10) and sexual behavior (11), as well as effects on controlling pain threshold (12, 13) and in the pathogenesis of Alzheimer's disease (14).Studies involving L-Ala-substituted analogues of galanin have identified Trp-2, Asn-5, and Tyr-9 as well as the N-terminal amino group as being critical determinants for receptor binding. These amino acids are located in the N-terminal helical part of galanin that it is made up of the same 15 aa in all species from which it was isolated (15, 16). Fragments of galanin have shown low binding affinity but these peptides are vulnerable to the action of the peptidases and unable to cross the blood-brain barrier (17,18). Two nonpeptide antagonists of the galanin receptor have been reported, spirocoumaranon (Sch202596) (19) and 2,3-dihydro-2-(4-methylphenyl)-1,4-dithiepin-1,1,4,4-tetroxide (20) (see Fig. 1), but there is only one nonpeptide galanin receptor ligand, galnon, that shows agonist activity (21).In this study, we report an example of a nonpeptide subtype selective agonist for the galanin receptor, galmic, discovered by application of a combinatorial library approach (22). MethodsExperimental. Reactions were performed under an argon atmosphere, NMR spectra were recorded on a Bruker DRX 600 spectrometer (unless otherwise mentioned), and the chemical shifts are given in ppm relative to tetramethylsilane. The spectra were referenced to deuterated solvents indicated in brackets in the analytical data. High-resolution MALDI-Fourier transform MS (FTMS) measurements were performed on an IonSPec (Lake Forest, CA) FTMS mass spectrometer by using 2,5-dihydroxybenzoic acid as the matrix. For TLC, silica plates IB2-F (J. T. Baker) were used. For column chromatography, silica gel 60, 230-400 mesh (Merck) was used. Preparative chromatographic plates and silica gel 60 F 254 (20 ϫ 20 cm, 0.5 mm) were used. Anhydrous solvents and chemicals were used as purchased from commercial suppliers. General Procedures. ...

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Avian galanin: Cloning of complementary DNAs and characterization of transcripts in different tissues

Kohchi

Tsutsui

2000

J. Exp. Zool.

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Human galanin: Primary structure and indentification of two molecular forms

Cited by 117 publications

References 18 publications

A preprogalanin cDNA from the turtle pituitary and regulation of its gene expression

A preprogalanin cDNA from the turtle pituitary and regulation of its gene expression

Synthesis of galmic: A nonpeptide galanin receptor agonist

Avian galanin: Cloning of complementary DNAs and characterization of transcripts in different tissues

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