Galanin (1-30) (human)

The neuropeptide galanin (Gal) and its receptors (GalR1, GalR2, and GalR3) are expressed in spinal cord. We have characterized the pharmacology of the antinociceptive effects of intrathecally (i.t.) administered galanin and its analogs in the formalin test in rats, using an automated flinch detection system. Intrathecal injection of rat galanin (Gal(1-29)) or human galanin (Gal(1-30)) produced a dose-dependent inhibition of formalin-evoked flinching in phase 2, but not in phase 1. Relative potency of galanin homologs is Gal(1-29) >or= Gal(1-30) > galanin-like peptide(1-24) >or= Gal(2-11) = Gal (3-29) (an inactive analog). Galanin(1-29) and Gal(1-30) are both high-affinity agonists to GalR1/R2, whereas Gal(2-11) is a GalR2 receptor agonist. Our data suggest that i.t. galanin-produced antinociception is mediated by activation of GalR1 receptors. When comparing antinociceptive effects of i.t. Gal(1-29) to morphine and to 2-amino-5-phosphonopentanoic acid (AP-5, an N-methyl-d-aspartate antagonist), Gal(1-29) is of intermediate potency between these two analgesic agents based on the ED(50) values. An isobolographic analysis showed synergy between Gal(1-29) and morphine and between Gal(1-29) and AP-5 on the second phase. Fixed ratio dose combinations of morphine and Gal(1-29), or AP-5 and Gal(1-29) produced significantly greater antinociception than predicted from simple additivity. In summary, the present findings reveal that 1) spinal galanin produces a reliable inhibition of formalin-induced facilitated nociceptive processing, an effect possibly mediated by GalR1 receptors; and 2) galanin potentiates i.t. morphine and AP-5-induced antinociception.

Intravenous injection of galanin increases plasma growth hormone (GH) and prolactin (PRL) concentrations. In the rat, the effects of galanin on GH appear to be mediated via the hypothalamic galanin receptor GAL-R(1), at which galanin-(3-29) is inactive. In contrast, the effect of galanin on PRL is mediated via the pituitary-specific galanin receptor GAL-R(W), at which galanin-(3-29) is fully active. We investigated the effects of an intravenous infusion of human galanin (hGAL)-(1-30) and -(3-30) on anterior pituitary hormone levels in healthy females. Subjects were infused with saline, hGAL-(1-30) (80 pmol. kg(-1). min(-1)), and hGAL-(3-30) (600 pmol. kg(-1). min(-1)) and with boluses of gonadotropin-releasing hormone, thyrotropin-releasing hormone, and growth hormone-releasing hormone (GHRH). Both hGAL-(1-30) and -(3-30) potentiated the rise in GHRH-stimulated GH levels [area under the curve (AUC), saline, 2,810 +/- 500 vs. hGAL-(1-30), 4,660 +/- 737, P < 0.01; vs. hGAL-(3-30), 6, 870 +/- 1,550 ng. min. ml(-1), P < 0.01]. In contrast to hGAL-(1-30), hGAL-(3-30) had no effect on basal GH levels (AUC, saline, -110 +/- 88 vs. hGAL 1-30, 960 +/- 280, P < 0.002; vs. hGAL-(3-30), 110 +/- 54 ng. min. ml(-1), P = not significant). These data suggest that the effects of galanin on basal and stimulated GH release are mediated via different receptor subtypes and that the human equivalent of GAL-R(W) may exist.

Galanin is a peptide hormone which modulates a wide variety of physiological processes, including secretion, muscle contraction, cognitive function, the reproductive axis, and feeding. Two galanin receptor subtypes, GalR1 and GalR2, have been cloned; however, for GalR2 only the rat sequence has been reported in the literature. Our cloning of human GalR2 reveals its amino acid sequence to be 85% identical to rat GalR2 and 39% identical to human GalR1. Binding of [125I]galanin to the human GalR2 receptor transiently expressed in COS-7 cells was saturable (Kd = 0.24 nM +/- 0.06 nM) with a receptor density of 383 +/- 66 fmol/mg protein. Human galanin(1-30) bound with high affinity to the human GalR2 receptor, with a Ki value of 0.86 +/- 0.12 nM. With the identification of a second galanin receptor subtype, the specific functions of human galanin receptor subtypes can now begin to be addressed.