galanin-like-peptide and Pain

The galanin peptide family consists of the "parental" galanin, galanin-message-associated peptide (GMAP) which derives from the same peptide precursor gene product as galanin, galanin-like peptide (GALP) encoded by a different gene, and the recently discovered peptide alarin which is encoded by a splice variant of the GALP gene. The galanin receptor family currently comprises 3 members, GalR1, GalR2, and GalR3, which are all G-protein-coupled receptors. This review will provide an overview of the comprehensive, pharmacological characterization of endogenous and synthetic galanin receptor ligands and their interactions with the galanin receptors, a summary of the various (pleiotropic) biological actions of galanin and GALP (and alarin), and briefly discuss the implications of pathological changes for health and disease and potential clinical therapeutics. Since its discovery more than 20 years ago, a large number of putative physiological functions have been ascribed to galanin, and active research still continues to validate these functions and determine their importance for physiology and pathology. Since the more recent identification of GALP, considerable research has identified functions for this peptide in the central nervous system (CNS), but the identity of its preferred, native receptor is still unknown. Little is known of the role of alarin apart from evidence of its expression and a vasoactive action in the skin. The wide range of functions of the galanin peptide family indicates an essential role for galanin signaling in "mind and body homeostasis" and a potential therapeutic efficacy in a variety of human diseases, particularly epilepsy, Alzheimer's disease, and diabetes.

Topics: Alzheimer Disease; Animals; Brain; Diabetes Mellitus; Epilepsy; Galanin; Galanin-Like Peptide; Gastrointestinal Tract; Humans; Ligands; Neoplasms; Organ Specificity; Pain; Peptide Fragments; Peripheral Nervous System; Receptors, Galanin; Skin

Topics: Alzheimer Disease; Amino Acid Sequence; Animals; Digestive System; Digestive System Physiological Phenomena; Galanin-Like Peptide; Humans; Mental Disorders; Molecular Sequence Data; Muscle, Smooth; Nerve Tissue Proteins; Pain; Pancreas; Pituitary Hormones; Receptors, Galanin; Receptors, Neuropeptide

Galanin-like peptide (GALP) was recently isolated from the porcine hypothalamus. The GALP mRNA is restricted in the hypothalamic arcuate nucleus and pituicytes in the posterior pituitary grand (PP) of the rat. The physiological function of the GALP is not clear in both areas. We focused on the regulation of the GALP gene expression to determine the role of GALP in the PP. We examined the effects of potent stressors to modulate a pituitary function, nociceptive stimuli and acute and chronic inflammatory stresses on the expression of the GALP gene in the PP using in situ hybridization histochemistry. Subcutaneous (s.c.) injection of 5% formalin in the bilateral hind paws caused a moderate increase of GALP gene expression in the PP. Intraperitoneal (i.p.) injection of lipopolysaccharide (LPS) also caused a marked increase of GALP gene expression in the PP. Effects of i.p. injection of LPS on the expression of the GALP gene in the PP were attenuated by pretreatment with i.p. injection of indomethacin. The levels of GALP mRNA in the PP were markedly increased by two peaks at 24 h and 15 days after s.c. injection of heat-inactivated M. butyricum that induced adjuvant arthritis. These results suggested that inflammatory stresses may be a potent stimulant to induce the expression of the GALP gene in the PP.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Experimental; Dehydration; Galanin-Like Peptide; Gene Expression Regulation; Lipopolysaccharides; Male; Nerve Tissue Proteins; Osmotic Pressure; Pain; Pain Measurement; Pituitary Gland, Posterior; Rats; Rats, Wistar; RNA, Messenger; Shock, Septic; Stress, Physiological