Galanin-receptor ligand M40 peptide distinguishes between putative galanin-receptor subtypes.
The galanin-receptor ligand M40 [galanin-(1-12)-Pro3-(Ala-Leu)2-Ala amide] binds with high affinity to [mono[125I]iodo-Tyr26]galanin-binding sites in hippocampal, hypothalamic, and spinal cord membranes and in membranes from Rin m5F rat insulinoma cells (IC50 = 3-15 nM). Receptor autoradiographic studies show that M40 (1 microM) displaces [mono[125I]iodo-Tyr26]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 galanin on feeding, and it blocks the galaninergic inhibition of the scopolamine-induced acetylcholine release in the ventral hippocampus in vivo. In contrast, M40 completely fails to antagonize both the galanin-mediated inhibition of the glucose-induced insulin release in isolated mouse pancreatic islets and the inhibitory effects of galanin on the forskolin-stimulated accumulation of 3',5'-cAMP in Rin m5F 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 galanin receptor may exist. Hypothalamic and hippocampal galanin receptors represent a putative central galanin-receptor subtype (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.
Bartfai
T
T
Department of Neurochemistry and Neurotoxicology, Arrhenius Laboratories, Stockholm University, Sweden.
Langel
U
U
Bedecs
K
K
Andell
S
S
Land
T
T
Gregersen
S
S
Ahrén
B
B
Girotti
P
P
Consolo
S
S
Corwin
R
R
D000595:Amino Acid Sequence; D000818:Animals; D001667:Binding, Competitive; D005247:Feeding Behavior / Q000502:physiology; D019004:Galanin; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D008024:Ligands; D008297:Male; D008969:Molecular Sequence Data; D010446:Peptide Fragments; D010455:Peptides / Q000378:metabolism* / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D044088:Receptors, Galanin; D011964:Receptors, Gastrointestinal Hormone / Q000145:classification* / Q000378:metabolism; D012636:Secretory Rate / Q000187:drug effects
D007328:Insulin; D008024:Ligands; C079517:M40; D010446:Peptide Fragments; D010455:Peptides; D044088:Receptors, Galanin; D011964:Receptors, Gastrointestinal Hormone; D019004:Galanin