Galanin and galanin antagonists: molecular and biochemical perspectives.
The neuropeptide galanin potently inhibits insulin release, hippocampal acetylcholine release and firing of locus coeruleus cells, and stimulates feeding and release of growth hormone. Galanin regulates K+ channels, adenylyl cyclase and phospholipase C by acting at Gi/Go protein-coupled high-affinity receptors. Galanin receptor agonists such as the N-terminal fragment galanin1-16 act synergistically with morphine in the somatosensory system and have potential analgetic application. Galanin antagonists may be useful therapeutic agents in endocrinology, neurology and psychiatry. The enhancing effect of such agents on hippocampal cholinergic function would be useful in treatment of Alzheimer's disease. Recent synthesis of a series of high-affinity galanin antagonists, reviewed, along with galanin's actions, by Tamas Bartfai and colleagues, opens the possibility of examining the functions of endogenous galanin and test the pharmacological usefulness of antagonism of galanin function in the endocrine, somatosensory and central nervous systems.
Bartfai
T
T
Department of Neurochemistry and Neurotoxicology, Stockholm University, Sweden.
Fisone
G
G
Langel
U
U
D000109:Acetylcholine / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D019004:Galanin; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D008969:Molecular Sequence Data; D009479:Neuropeptides / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D010455:Peptides / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D044088:Receptors, Galanin; D011964:Receptors, Gastrointestinal Hormone / Q000378:metabolism; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism; D013329:Structure-Activity Relationship
D007328:Insulin; D009479:Neuropeptides; D010455:Peptides; D044088:Receptors, Galanin; D011964:Receptors, Gastrointestinal Hormone; D019004:Galanin; D000109:Acetylcholine