CEREBROMICROVASCULAR ENDOTHELIAL CULTURE--CHOLINERGIC & HISTAMINERGIC RECEPTORS

乙酰胆碱和组胺是已知的血管活性物质， 参与调节脑血流量（CBF）和/或血脑 屏障（BBB）功能。这一假设已得到检测的支持 胆碱能纤维和组胺能纤维在大脑皮层附近 船舶.此外，这两种物质的受体在 从动物脑中分离的微血管，但不从人中分离。 本研究旨在检测乙酰胆碱、卡巴胆碱 和组胺对内皮细胞中腺苷酸环化酶（AC）活性的影响 来源于人类微血管的三个部分。 腺苷酸环化酶对乙酰胆碱、卡巴胆碱和 在所有检测的内皮组织匀浆中均可见组胺（4 - 11 通道）源自大微血管。哌仑西平（M1-毒蕈碱 抑制剂）阻断了乙酰胆碱和卡巴胆碱刺激的 环磷酸腺苷（cAMP），而甲氧六明（M2毒蕈碱抑制剂）对AC无影响 内皮细胞来源于大的微血管。初步调查 证明了cAMP产生的剂量依赖性胆碱能刺激 在毛细血管和小微血管的内皮细胞中。的 内皮AC活性对组胺的反应被抑制（30-100%） 西咪替丁表明AC与H2受体连接。这些发现 首次证明了胆碱能和组胺能 受体连接到AC系统在血管微血管内皮细胞 人脑 由于有毒的人血清导致的内皮细胞培养物的损失阻止了 完成这个项目。

Acetylcholine and histamine are known as vasoactive substances which may be involved in regulating cerebral blood flow (CBF) and/or blood-brain barrier (BBB) functions. This supposition has been supported by detection of cholinergic and histaminergic fibers in the close vicinity of cerebral vessels. Moreover, receptors for both substances were described in microvessels isolated from brain of animals but not from man. The aim of this investigation was to examine the effect of acetylcholine, carbachol and histamine on adenylate cyclase (AC) activity in the endothelium derived from three fractions of human microvessels. The response of adenylate cyclase to acetylcholine, carbachol and histamine was seen in all examined homogenates of endothelium (4th-11th passage) derived from large microvessels. Pirenzepine (M1-muscarinic inhibitor) blocked the acetylcholine and carbachol stimulated formation of cAMP while methoctramine (M2 muscarinic inhibitor) had no effect on AC of endothelium derived from large microvessels. Preliminary investigations demonstrated a dose-dependent cholinergic stimulation of cAMP production in endothelium derived from capillaries and small microvessels. The response of endothelial AC activity to histamine was inhibited (30-100%) by cimetidine indicating the AC linkage to H2-receptors. These findings represent the first demonstration of cholinergic and histaminergic receptors linked to the AC system in cerebromicrovascular endothelium of human brain. The loss of endothelial cultures due to toxic human serum prevented the completion of this project.