Galanin analogues: agonist and antagonist.
23 galanin-related peptides were synthesized by solid phase technology or conventional solution method. The purity of the products was carefully assessed by routine analytical criteria. Using these synthetic peptides, we have investigated the effects of galanins and structurally modified galanin peptides on glucose-stimulated insulin release using the isolated perfused rat pancreas, gastrin and somatostatin release using the isolated perfused rat stomach, the neurally-evoked muscle contractions in guinea pig ileum and the C-fiber response in the isolated spinal cord of the new born rat. The results suggest that the galanin amino-terminal 1-15 sequence is crucial for its activity in the above four systems. With the goal of developing a specific antagonist of galanin, synthetic galanin (1-15) analogues [D-Thr6,D-Trp8,9]galanin(1-15)ol, and [D-Trp8,9]galanin(1-15)ol were found to be a potent antagonist for inhibitory effect of galanin on glucose-induced insulin release.
Yanaihara
N
N
University of Shizuoka, School of Pharmaceutical Sciences, Japan.
Mochizuki
T
T
Takatsuka
N
N
Iguchi
K
K
Sato
K
K
Kakuyama
H
H
Li
M
M
Yanaihara
C
C
D000595:Amino Acid Sequence; D000818:Animals; D019004:Galanin; D005753:Gastric Mucosa / Q000187:drug effects / Q000378:metabolism*; D005755:Gastrins / Q000378:metabolism; D006168:Guinea Pigs; D006801:Humans; D007082:Ileum / Q000187:drug effects / Q000502:physiology; D007202:Indicators and Reagents; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008969:Molecular Sequence Data; D009119:Muscle Contraction / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology; D009479:Neuropeptides / Q000138:chemical synthesis / Q000494:pharmacology*; D010455:Peptides / Q000138:chemical synthesis / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D017386:Sequence Homology, Amino Acid; D013004:Somatostatin / Q000378:metabolism; D013329:Structure-Activity Relationship; D013552:Swine
D005755:Gastrins; D007202:Indicators and Reagents; D007328:Insulin; D009479:Neuropeptides; D010455:Peptides; D013004:Somatostatin; D019004:Galanin