MODULATION OF NOREPINEPHRINE RELEASE BY GALANIN IN RAT MEDULLA-OBLONGATA

Galanin, a 29-amino acid peptide, is widely distributed in both the central and peripheral nervous systems and is colocalized with catecholamines, although its physiological significance remains to be elucidated. In the present study we investigated the regulatory mechanisms of galanin on norepinephrine release in rat medulla oblongata. In slices of medulla oblongata of Sprague-Dawley rats, galanin inhibited the stimulation-evoked [H-3]norepinephrine release in a concentration-dependent manner (fractional release ratio during electrical stimulation: control 0.937+/-0.043, mean+/-SEM, n=6; galanin 1 x 10(-7) M 0.501+/-0.037, n=6, p<0.05; and galanin 1 x 10(-6) M 0.299+/-0.018 n=6, p<0.05). Galanin potentiated inhibition of [H-3]norepinephrine release by the alpha-2-agonists (UK 14,304 and clonidine). The blockade of alpha-2-adrenergic receptors by RX 781094 diminished the inhibition of norepinephrine release by galanin. Pretreatment of pertussis toxin, which interferes with the coupling of inhibitory guanosine triphosphate-binding proteins to adenylate cyclase, significantly attenuated the suppressive effects of galanin on norepinephrine release. In slices of medulla oblongata obtained from spontaneously hypertensive rats (SHR), the inhibitory effect of galanin on norepinephrine release was significantly less than in those from age-matched Wistar-Kyoto rats. These results show that galanin might inhibit the stimulation-evoked norepinephrine release in rat medulla oblongata, at least partially mediated by alpha-2-adrenergic receptors and the pertussis toxin-sensitive guanosine triphosphate-binding proteins. Moreover, less suppression of norepinephrine release by galanin in SHR suggests that galanin might be involved in the regulation of central sympathetic nervous activity in hypertension.