THE NOVEL HIGH-AFFINITY ANTAGONIST, GALANTIDE, BLOCKS THE GALANIN-MEDIATED INHIBITION OF GLUCOSE-INDUCED INSULIN-SECRETION

被引：91

作者：

LINDSKOG, S

AHREN, B

LAND, T

LANGEL, U

BARTFAI, T

机构：

[1] UNIV STOCKHOLM,DEPT BIOCHEM,ARRHENIUS LABS,S-10691 STOCKHOLM,SWEDEN

[2] UNIV LUND,DEPT SURG,S-22101 LUND,SWEDEN

[3] UNIV LUND,DEPT PHARMACOL,S-22101 LUND,SWEDEN

来源：

EUROPEAN JOURNAL OF PHARMACOLOGY | 1992年 / 210卷 / 02期

关键词：

GALANIN; GALANIN RECEPTOR ANTAGONISTS; INSULIN SECRETION; GALANTIDE; (DISPLACEMENT);

D O I：

10.1016/0014-2999(92)90669-U

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

This study describes the synthesis and effects of the first antagonist to the widely distributed neuropeptide, galanin, which inhibits the secretion of insulin. The first galanin antagonist is a 20-amino acid-long chimeric peptide of the composition galanin-(1-12)-Pro-substance P-(5-11) amide: Gly-Trp-Thr-Leu-Asn-Ser-Ala-Gly-Tyr-Leu-Leu-Gly-Pro-Gln-Gln-Phe-Phe-Gly-Leu-Met amide. The peptide dose dependently (IC50 = 1.0 nM) antagonizes the galanin-mediated inhibition of the glucose-induced insulin secretion from mouse pancreatic islets. The antagonist was also found to displace I-125-monoiodo-[Tyr26]galanin from membranes of the insulin producing Rin m 5F cells with an IC50 value of less than 0.1 nM. The antagonist is named galantide.

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页码：183 / 188

页数：6

相关论文

共 20 条

[1]

AMIRANOFF B, 1989, J BIOL CHEM, V264, P20714

[2] PROCEDURE BASED ON STATISTICAL CRITERIA FOR DISCRIMINATION BETWEEN STEADY-STATE KINETIC MODELS [J].

BARTFAI, T ;

MANNERVI.B .

FEBS LETTERS, 1972, 26 (01) :252-+

[3] BIOLOGICAL-ACTIVITY OF C-TERMINAL PARTIAL SEQUENCES OF SUBSTANCE-P [J].

BURY, RW ;

MASHFORD, ML .

JOURNAL OF MEDICINAL CHEMISTRY, 1976, 19 (06) :854-856

[4] GALANIN HYPERINNERVATES SURVIVING NEURONS OF THE HUMAN BASAL NUCLEUS OF MEYNERT IN DEMENTIAS OF ALZHEIMERS AND PARKINSONS-DISEASE - A HYPOTHESIS FOR THE ROLE OF GALANIN IN ACCENTUATING CHOLINERGIC DYSFUNCTION IN DEMENTIA [J].

CHANPALAY, V .

JOURNAL OF COMPARATIVE NEUROLOGY, 1988, 273 (04) :543-557

[5] GALANIN - SYMPATHETIC NEUROTRANSMITTER IN ENDOCRINE PANCREAS [J].

DUNNING, BE ;

TABORSKY, GJ .

DIABETES, 1988, 37 (09) :1157-1162

[6] N-TERMINAL GALANIN-(1-16) FRAGMENT IS AN AGONIST AT THE HIPPOCAMPAL GALANIN RECEPTOR [J].

FISONE, G ;

BERTHOLD, M ;

BEDECS, K ;

UNDEN, A ;

BARTFAI, T ;

BERTORELLI, R ;

CONSOLO, S ;

CRAWLEY, J ;

MARTIN, B ;

NILSSON, S ;

HOKFELT, T .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1989, 86 (23) :9588-9591

[7] GALANIN INHIBITS ACETYLCHOLINE-RELEASE IN THE VENTRAL HIPPOCAMPUS OF THE RAT - HISTOCHEMICAL, AUTORADIOGRAPHIC, INVIVO, AND INVITRO STUDIES [J].

FISONE, G ;

WU, CF ;

CONSOLO, S ;

NORDSTROM, O ;

BRYNNE, N ;

BARTFAI, T ;

MELANDER, T ;

HOKFELT, T .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1987, 84 (20) :7339-7343

[8] CONTINUOUS, CLONAL, INSULIN-SECRETING AND SOMATOSTATIN-SECRETING CELL-LINES ESTABLISHED FROM A TRANSPLANTABLE RAT ISLET CELL TUMOR [J].

GAZDAR, AF ;

CHICK, WL ;

OIE, HK ;

SIMS, HL ;

KING, DL ;

WEIR, GC ;

LAURIS, V .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES, 1980, 77 (06) :3519-3523

[9] GALANIN-INDUCED INHIBITION OF INSULIN-SECRETION FROM RAT ISLETS - EFFECTS OF RAT AND PIG GALANIN AND GALANIN FRAGMENTS AND ANALOGS [J].

GREGERSEN, S ;

HERMANSEN, K ;

LANGEL, U ;

FISONE, G ;

BARTFAI, T ;

AHREN, B .

EUROPEAN JOURNAL OF PHARMACOLOGY, 1991, 203 (01) :111-114

[10] COATED CHARCOAL IMMUNOASSAY OF INSULIN [J].

HERBERT, V ;

LAU, KS ;

GOTTLIEB, CW ;

BLEICHER, SJ .

JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 1965, 25 (10) :1375-+