SUBSTANCE P IN CARDIOVASCULAR REGULATION

P 物质在心血管调节中的作用

• 批准号: 3345500
• 负责人: JOHN M STEWART
• 金额: $ 14.15万
• 依托单位: UNIVERSITY OF COLORADO DENVER
• 依托单位国家: 美国
• 财政年份: 1990
• 资助国家: 美国
• 起止时间: 1990-04-01 至 1993-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3345500
• 关键词: autonomic reflex; baroreceptors; blood pressure; calcitonin gene related peptide; central nervous system; endopeptidases; glutamates; high performance liquid chromatography; hypertension; inhibitor /antagonist; laboratory rat; microinjections; neural transmission; neuropeptide Y; neuropharmacology; peptide chemical synthesis; protein structure function; stimulant /agonist; substance P; tachykinin

This project studies the role of the neuropeptide substance P (SP) in CNS regulation of blood pressure and possible abnormalities of this system in hypertension. Much evidence supports a role for SP as a neurotransmitter or neuromodulator of the baroreflex arc, the principal mechanism for instantaneous physiological regulation of blood pressure. SP apparently functions in this system at both afferent and efferent levels. SP appears to exert its neurotransmitter and/or neuromodulator effects in the CNS only after processing by enzymes which yield active N-terminal or C-terminal fragments. The N-terminal fragment SP(1-7) is produced by the endopeptidase 3.4.24.11 and appears to be a neurotransmitter for afferents from the carotid sinus and aortic arch which terminate in the nucleus tractus solitarius (NTS), while the C-terminal fragment SP(5-11) is produced by the post-proline cleaving enzyme and elevates blood pressure by stimulation of sympathetic outflow. SP(1-7) fulfills many of the criteria for being a neurotransmitter in the baroreflex arc. This project studies the role(s) of SP(1-7) in this system. Peptides related to SP(1-7) are synthesized in the search for antagonists and potent, long-acting agonists. These peptides are injected into the NTS to study their effect on blood pressure and functioning of the baroreflex. Antisera against the peptides and the processing enzymes will also be used. Other tachykinins and the neuropeptides calcitonin gene related peptide (CGRP) and neuropeptide Y (NPY) will also be studied. Interaction of SP and SP(1-7) with glutamate, which also fulfills many criteria for a neurotransmitter in this system, will be studied with specific glutamate agonists and antagonists. Other candidate neurotransmitter amino acids will also be studied.

本课题研究神经肽P物质(SP)在中枢神经系统中的作用 高血压的调节和这一系统可能的异常 高血压。许多证据支持SP作为神经递质或 压力反射弧的神经调节剂，其主要机制是 血压的瞬时生理调节。SP显然 在这个系统中，有传入和传出两个层面的功能。出现SP 仅在中枢神经系统发挥神经递质和/或神经调质作用 经过产生活性N-端或C-端的酶处理后 碎片。N-末端片段SP(1-7)由内肽酶产生 3.4.24.11，似乎是来自 终止于束核的颈动脉窦和主动脉弓 Solitarius(NTS)，而C-末端片段SP(5-11)由 后脯氨酸裂解酶和通过刺激 感同身受的流出。SP(1-7)符合成为 压力反射弧区的神经递质。 本课题研究SP(1-7)在这一体系中的角色(S)。肽类 与SP(1-7)有关的化合物是在寻找拮抗剂和 强效、长效激动剂。这些多肽被注射到NTS中以 研究它们对血压和压力感受器反射功能的影响。 还将使用针对多肽和加工酶的抗血清。 其他速激肽和神经肽降钙素基因相关肽 还将研究降钙素基因相关肽(CGRP)和神经肽Y(NPY)。SP与互联网的相互作用 SP(1-7)和谷氨酸，它也符合许多标准 这个系统中的神经递质将用特定的谷氨酸进行研究 激动剂和拮抗剂。其他候选神经递质氨基酸将 也有待研究。