Galanin在大鼠環導水管灰質腦切片的電生理研究

1. Galanin在人體是一種含30個amino acids的neuropeptide，而在大鼠galanin 則含有29個amino acids。許多實驗證實，galanin參與了許多生理反應，包括取食行為、性行為、賀爾蒙分泌、胃腸蠕動與分泌，以及痛覺調控。Galanin參與在痛覺調控的研究，多半見於脊椎層次而鮮少於supraspinal層次當中。 2. Galanin以腦腔室路徑給予，被報導能夠增強嗎啡所引起的supraspinal止痛作用。當它注射在中腦環導水管灰質區 (PAG)，一個supraspinal中opioid引發麻醉反應的重要位置，它也能夠產生止痛作用。因而，我們想利用全細胞補綴記錄方式，在含PAG的腦切片中，研究galanin環導水管灰質腹側區 (vlPAG)神經細胞的細胞作用，以瞭解galanin在supraspinal層次中可能的止痛機制。同時也研究galanin與galantide之間的交互作用，其中galantide被認為是galanin受體拮抗劑。 3. Galanin在30到300 nM濃度下，並不能影響利用範圍由-60到-140 mV的hyperpolarization ramp所引發的膜電流，而此研究方式是在瞭解vlPAG神經細胞中，藥物是否能夠活化G-protein結合的內向整流型鉀離子通道 (GIRK)。 4. 在vlPAG腦區的同一顆神經細胞中，當給予區域性的刺激，引發在-70 mV下記錄到的EPSCs，以及在0 mV的IPSCs。所記錄到的EPSCs大小 (41

關鍵字

Galanin ；環導水管灰質區；神經傳遞；鉀離子通道

並列摘要

1. Galanin, a neuropeptide consisting of 29- (rat) or 30- (human) amino acids, has been reported to be involved in many physiological functions, including feeding, sexual behavior, hormone secretion, GI motility/secretion, and pain regulation. The effects of galanin involved in pain regulation have been actively explored in the spinal, but less in the supraspinal level. 2. Galanin has been reported to potentiate the supraspinal antinociception induced by morphine when administrated intraventricularly. It also produced antinociception when it was injected into the midbrain periaqueductal gray (PAG), a crucial area for supraspinal analgesia induced by opioids. We, therefore, investigated cellular actions of galanin in the ventrolateral PAG (vlPAG) neurons to elucidate the possible supraspinal antinociceptive mechanisms of galanin using the whole cell patch-clamp recording technique in brain slices containing the PAG. The interactions of galanin with galantide, a putative galanin receptor antagonist, were also studied. 3. Galanin at 30~300 nM, did not affect the membrane current elicited by a hyperpolarization ramp from -60 to -140 mV, which was applied to evaluate if drugs would activate G-protein coupled inwardly rectifying K+ (GIRK) channels in vlPAG neurons. 4. When local stimulation evoked EPSCs and IPSCs were recorded in the same neuron of the vlPAG at -70 and 0 mV, respectively, the amplitude of EPSCs (41

並列關鍵字

PAG ； Galanin ； synaptic transmission ； GIRK

參考文獻

Aimone LD, Gebhart GF (1986) Stimulation-produced spinal inhibition from the midbrain in the rat is mediated by an excitatory amino acid neurotransmitter in the medial medulla. J Neurosci 6:1803-1813.

Albin RL, Makowiec RL, Hollingsworth Z, Dure LSt, Penney JB, Young AB (1990) Excitatory amino acid binding sites in the periaqueductal gray of the rat. Neurosci Lett 118:112-115.

Amiranoff B, Lorinet AM, Yanaihara N, Laburthe M (1989) Structural requirement for galanin action in the pancreatic beta cell line Rin m 5F. Eur J Pharmacol 163:205-207.

Argiolas A (1999) Neuropeptides and sexual behaviour. Neurosci Biobehav Rev 23:1127-1142.

Bartfai T, Fisone G, Langel U (1992) Galanin and galanin antagonists: molecular and biochemical perspectives. Trends Pharmacol Sci 13:312-317.

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Galanin在大鼠環導水管灰質腦切片的電生理研究

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