Advanced Targeting Systems (ATS) has just been awarded a $100,000 research grant from the National Institute on Drug Abuse (NIDA). This Phase I SBIR (Small Business Innovation Research) grant proposes to develop a research reagent to study the function of the neuropeptide, galanin. This will be an important tool for scientists to use in the study of galanin’s influence in many biological systems: pain, depression, anxiety, memory and feeding.
Galanin is a 29/30 amino acid peptide and asserts its biological effect through G-protein-coupled receptors that are widely distributed. In the brain, I125-galanin or galanin- analog binding studies show high levels of binding in the cerebral cortex, thalamus, pons, and cerebellum. Outside the brain, the anterior pituitary, pituitary tumors, astrocytes, spinal cord, and gastric and jejunal smooth muscle show ligand binding (1).
At the molecular level, multiple second messenger pathways are activated: inhibition of cyclic AMP, activation of channels including ATP- sensitive K+ channels, inhibition of L-type and N-type calcium channels, stimulation of inositol phospholipid turnover, stimulation and inhibition of calcium mobilization, stimulation of phospholipase A2, activation of MAP kinase, mitogenesis and stimulation of cyclic AMP accumulation (1).
This diversity of biochemical activities leads to a wide array of effects in biological systems. Galanin is reported to modulate feeding and sexual behavior, play a role in pain transmission, affect depression, and may be involved in the pathogenesis of Alzheimer’s disease (2).
For the next six months, ATS will develop and test a galanin-saporin fusion protein to be offered commercially to research scientists worldwide. This targeted toxin will be a valuable research tool to study biological systems and for the study of drug abuse. The presence of galanin receptor-expressing cells in systems that control depression, pain and eating disorders, along with the connection between the opiate receptors, may indicate that galanin plays a role in drug abuse. The removal of these neurons, and their effects on neurons that express opiate receptors, will be a powerful tool to examine the role of galanin in drug use and abuse.
1. Williams RL; Hilton DJ; Pease S; Willson TA; Stewart CL; Gearing DP; Wagner EF; Metcalf D; Nicola NA; Gough NM. Nature 1988, 336, 684-687.
2. Kask K; Berthold M; Bartfai T. Life Sci. 1997, 60 (18), 1523-1533.