Biochemical Events Coupled to the Activation of Serotonin Receptors in Brain Regions of the Rat

探討大白鼠不同腦區域中活化血清素受體所引發之生化反應

魏健吾(Jiann-Wu Wei) ； 李銘仁(Ming-Jen Lee) ； 葉世榮(Shin-Rung Yeh)

《The Chinese Journal of Physiology》 34卷4期 (1991/12) Pp. 387-398

摘要

本研究係探討大白鼠不同腦區域中活化血清素受體所引發之磷酸化肌醇及環狀腺核苷酸之變化情形。不同區域腦組織之切片，經由血清素處理後，可以促成磷酸化肌醇之量，在大腦皮質，海馬迴，中腦及腦幹上有明顯的增加。然而，在小腦上則無顯著的變化。血清素本身對於環狀腺核苷酸之基礎量，在大部分之腦區域中並無明顯的作用，然而在中腦切片則有明顯的增加作用。但是血清素對於forskolin促成環狀腺核苷酸之增加則有抑制作用。在大腦皮質及腦幹此抑制作用很明顯，但對於海馬迴及小腦之切片，則此抑制作用並不明顯。血清素所引發的兩種生化反應，依其濃度之增加而變化程度加大，其劑量在10^(-4)與10^(-3)M間可達最大的反應。在高劑量下(10^(-4)M)，血清素所引發自磷酸化肌醇之變化，以大腦皮質最明顯，海馬迴，中腦次之，腦幹之作用則再次之。在此劑量下之血清素具有抑制forskolin所引發環狀腺核苷酸的變化，此抑制作用以大腦皮質及腦幹較明顯，海馬迴及小腦等區域則不明顯。以上結果顯示血清素所引發此兩種生化反應，其程度因腦區域不同而異，此可能係由於血清素受體亞型之密度及分布，因區域不同所致。一般認為活化5HT1亞型受體，可以導致環狀腺核苷酸的降低，而活化5HT4亞型受體，則可以增加此核苷酸產量。此外，活化5HT2亞型受體，則可以增加磷酸化肌醇之產量，因上述之生化作用，可為專一性亞型受體拮抗劑所阻斷。

並列摘要

Wei, J.W., Mi. Lee, and S.R. Yeh, Biochemical events coupled to the activation of serotonin receptors in brain regions of the rat. Chinese J. Physiol. 34(4): 387-398, 1991. Effects of serotonin on the levels of inositol phosphate and cyclic AMP in certain brain regions of the rat were studied. When brain slices were treated with serotonin (10^(-4) or l0^(-5) M), it caused significant increases in inositol phosphate levels in cerebral cortex, hippocampus, midbrain and brain stem, but not in cerebellum. Serotonin itself did not have a significant effect on the basal levels of cAMP in most of these regions, except in midbrain in which it had stimulatory effect. However, serotonin also had significant inhibitory effect on forskolin-induced cAMP formation in cerebral cortex, hippocampus and brain stem but not in midbrain in which an increase instead. Effects of serotonin on both biochemical events were in dose-dependent manner, and their maximal responses were at doses between 10^(-4) and l0^(-3)M. The rank order of the maximal response to serotonin on inositol phosphate production in these regions was cerebral cortex＞ hippocampus＞ midbrain＞ brain stem ＞ cerebellum. On the other hand, the rank order of the maximal response to serotonin on inhibiting forskolin-induced cAMP formation was cerebral cortex = brain stem＞ hippocampus. Our data revealed that there is a regional difference in serotonin-induced inositol phosphate and cAMP responses. This difference is likely due to a differential distribution of serotonergic receptor subtypes and densities in different regions of rat brain.

並列關鍵字

serotonin receptor subtypes ； brain regions ； phosphoinositide turnover,cAMP formation