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Functional significance of PACAP receptors in regulating secretion and synthesis of vasopressi

PACAP受体在调节加压素分泌和合成中的功能意义

基本信息

批准号：
10680708
负责人：
SHIODA Seiji
金额：
$ 2.18万
依托单位：
Showa University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1998
资助国家：
日本
起止时间：
1998 至 1999
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10680708/
关键词：
PACAP Noradrenalin Vasopressin Siganal transduction Calcium channel Neuroendocrine cells Hypothalamus

项目摘要

PACAP-containing axon terminals innervate arginine-vasopressin (AVP)-containing neurons in the rat hypothalamic supraoptic nucleus (SON). PACAP receptor (PACAPR) mRNA was expressed at high-levels in SON expressed in AVP-containing neurons. Although the pathway arising from PACAP/NA (noradrenalin)-containing neurons in the ventrolateral medulla is involved in the regulation of AVP, the precise mechanism of action and physiological significance of the coexistence of PACAP and NA still need to be investigated. Both PACAP and NA induced large increases in the [Ca2+]I in isolated AVP-containing neurons. When PACAP and NA were added together, they evoked larger increase in [Ca2+]I in AVP neurons. An inhibitor of PKA completely inhibited the PACAP-induced increase in [Ca2+]I, and partly the NA-induced increase in AVP-containing neurons. We found that T-type calcium channels might contribute to Ca2+ influx during action potentials through cAMP-PKA signaling pathway and L-type currents might contribute to the generation of bursting activity. PACAP and NA, co-released from the same axon terminals, may act synergistically to stimulate calcium signaling in AVP neurons, which is mediated by both cAMP-PKA pathway and L-type Ca2+ channel. PACAP/NA may regulate the functions of AVP-containing neurons which participate in the control of plasma osmolarity and blood pressure.

大鼠下丘脑视上核(SON)内含有PACAP的轴突终末支配精氨酸加压素(AVP)神经元。PACAP受体(PACAPR)在SON中高水平表达于AVP阳性神经元。尽管延髓腹外侧区含有PACAP/NA(去甲肾上腺素)神经元的通路参与了AVP的调节，但PACAP和NA共存的确切作用机制和生理意义仍需进一步研究。PACAP和NA均可引起AVP神经元[Ca~(2+)]_i显著升高。当PACAP和NA共同作用时，AVP神经元内[Ca~(2+)]i的升高幅度更大。PKA抑制剂可完全抑制PACAP引起的[Ca~(2+)]i升高，部分抑制NA引起的含AVP神经元的升高。我们发现，在动作电位过程中，T型钙通道可能通过cAMP-PKA信号通路参与钙内流，L型电流可能参与爆发活动的产生。从同一轴突终末共同释放的PACAP和NA可能通过cAMP-PKA通路和L型钙通道协同刺激AVP神经元上的钙信号。PACAP/NA可调节AVP能神经元的功能，参与血浆渗透压和血压的控制。