Galanin (1-15) (porcine, rat)

The galanin receptor antagonist M40 blocks the central cardiovascular actions of the galanin N-terminal fragment (1-15).[Pubmed:10884520]

Eur J Pharmacol. 2000 Jul 7;399(2-3):197-203.

It has been shown that galanin plays a role in central cardiovascular regulation. Galanin administered centrally induces an increase of heart rate and a weak vasodepressor response, whereas the N-terminal galanin fragment (1-15) elicits vasopressor effects and tachycardia. Furthermore, it has been shown that galanin-(1-15), but not galanin-(1-29), decreases the baroreceptor reflex sensitivity. Since these data demonstrate that both galanin and its N-terminal fragment (1-15) exert a different modulation on central cardiovascular control, the aim of this work has been to study if the specific galanin receptor antagonist Galanin-(1-12)-Pro-(Ala-Leu)(2)-Ala]-amide (M40) could modulate their cardiovascular actions. Urethane anaesthetized rats were injected intracisternally and the changes in mean arterial pressure and heart rate were monitored. Two doses of M40 alone have been tested for their cardiovascular effects. With the dose of 1.0 nmol, a significant tachycardia was observed (P<0.001), but 0.1 nmol was ineffective. This suggests a possible agonistic effect for the higher doses of M40. The galanin receptor antagonist M40 at the dose of 0.1 nmol failed to modify the weak vasodepressor effects and tachycardia induced by 3.0 nmol of galanin-(1-29). However, the same dose completely blocked the vasopressor and tachycardic responses elicited by 3.0 nmol of galanin-(1-15). These data show that M40 differentially counteracts the central cardiovascular responses of the galanin fragment and give a functional support for the existence of galanin receptor subtypes within the brainstem. Therefore, the present findings can be explained on the basis that the cardiovascular actions of galanin-(1-29) could be mediated by one type of galanin receptor, whereas a galanin receptor subtype that recognizes N-terminal fragments of galanin may mediate the actions of galanin-(1-15).

Electrophysiological evidence for a hyperpolarizing, galanin (1-15)-selective receptor on hippocampal CA3 pyramidal neurons.[Pubmed:10588748]

Proc Natl Acad Sci U S A. 1999 Dec 7;96(25):14583-7.

The effects of the 29-amino acid neuropeptide galanin [GAL (1-29)], GAL(1-15), GAL(1-16), and the GAL subtype 2 receptor agonist D-tryptophan(2)-GAL(1-29) were studied in the dorsal hippocampus in vitro with intracellular recording techniques. GAL(1-15) induced, in the presence of tetrodotoxin, a dose-dependent hyperpolarization in hippocampal CA3 neurons. Most of the GAL(1-15)-sensitive neurons did not respond to GAL(1-29), GAL(1-16), or D-tryptophan(2)-GAL(1-29). These results indicate the presence of a distinct, yet-to-be cloned GAL(1-15)-selective receptor on CA3 neurons in the dorsal hippocampus.

Structural requirement for galanin action in the pancreatic beta cell line Rin m 5F.[Pubmed:2472967]

Eur J Pharmacol. 1989 Apr 12;163(1):205-7.

Galanin fragments were tested for their ability to alter forskolin-stimulated cyclic AMP production and insulin release from Rin m 5F cells. Galanin and its fragments inhibited both events with the following potencies: Gal-(1-29) greater than N-AcGal-(2-29) greater than Gal-(2-29) greater than Gal-(1-15). In contrast, Gal-(3-29), Gal-(10-29) and [Ile2]Gal were inactive. [Phe2]- and [Tyr2]Gal were moderately effective. We conclude that the N-terminal portion of galanin (in particular the aromatic amino acid in position 2) is crucial for activity.