Coexistence of three tachykinin receptors coupled to Ca++ signaling pathways in intestinal muscle cells.
Coexistence of three tachykinin receptors coupled to Ca++ signaling pathways in intestinal muscle cells.
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发表时间：
1994-07
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通讯作者：
P. Hellstrom;K. Murthy;J. Grider;G. Makhlouf
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作者：
P. Hellstrom;K. Murthy;J. Grider;G. Makhlouf
受体速激肽和信号通路，他们耦合的特点是分散的肌肉细胞从纵向肌肉层的大鼠肠。一种受体保护技术，其中选择性激动剂和拮抗剂被用来保护一个受体，而其他受体与N-乙基马来酰亚胺失活，使每个速激肽受体类型被分别确定。用选择性NK-1激动剂P物质甲酯或拮抗剂GR-82，334保护神经激肽（NK）-1受体（Glp-Ala-Asp-Pro-Asn-Lys-Phe-Tyr-D-Pro[spiro-gamma-lactamate]Leu-Trp-NH_2）能维持仅由P物质甲酯引起的收缩反应和胞浆游离Ca ~（++）（[Ca ~（++）]i）的增加;选择性NK-2激动剂β-[Ala 8]NKA（4-10）或选择性NK-2b拮抗剂L-659，877 [cyclo（Leu-Met-Gln-Trp-Phe-Gly）]，保留了仅由β-[Ala 8]NKA诱导的收缩反应和[Ca++]i的增加（4-10）;用选择性NK-3受体激动剂sanktide琥珀酰[Asp 6，MePhe 8] P物质（6-11）保护NK-3受体，仅保留琥珀酰[Asp 6，MePhe 8] P物质（6-11）诱导的收缩反应和[Ca++]i增加。当用作保护剂时，NK-2a拮抗剂MEN-10，376（H-Asp-Tyr-D-Trp-Val-D-Trp-D-Trp-Lys-NH 2）不保留对任何速激肽激动剂的应答。NK-1、NK-2和NK-3受体的保护分别完全保留了对优先内源性激动剂P物质、NKA和NKB的反应，但它们也部分保留了对非优先激动剂的反应（30-40%）。由于P物质和NKA是从肠肌肉组织中的相同前体共同释放的，因此该模式暗示了肌细胞对速激肽的收缩反应中存在相当大的稀疏性。使用选择性速激肽激动剂作为保护剂对分散的环形肌细胞的研究证实了三种速激肽受体类型的存在。结果表明，NK-1，NK-2b和NK-3受体的共存大鼠肠的肌肉细胞，优先激活的P物质，NKA和NKB，分别耦合到一个信号通路介导的收缩。
Receptors for tachykinins and the signaling pathway to which they are coupled were characterized in dispersed muscle cells from the longitudinal muscle layer of the rat intestine. A technique of receptor protection whereby selective agonists and antagonists were used to protect one receptor while other receptors were inactivated with N-ethylmaleimide enabled each tachykinin receptor type to be identified separately. Protection of neurokinin (NK)-1 receptors with the selective NK-1 agonist, substance P methylester, or antagonist, GR-82,334 (Glp-Ala-Asp-Pro-Asn-Lys-Phe-Tyr-D-Pro[spiro-gamma-lactam]Leu-Trp-NH2), preserved the contractile response and increase in cytosolic-free Ca++ ([Ca++]i) induced by substance P methylester only; protection of NK-2 receptors with the selective NK-2 agonist, beta-[Ala8]NKA(4-10), or the selective NK-2b antagonist, L-659,877 [cyclo(Leu-Met-Gln-Trp-Phe-Gly)], preserved the contractile response and increase in [Ca++]i induced by beta-[Ala8]NKA(4-10) only; and protection of NK-3 receptors with the selective NK-3 agonist, senktide succinyl-[Asp6,MePhe8]substance P(6-11), preserved the contractile response and increase in [Ca++]i induced by succinyl-[Asp6,MePhe8]substance P(6-11) only. When used as a protective agent, the NK-2a antagonist, MEN-10,376 (H-Asp-Tyr-D-Trp-Val-D-Trp-D-Trp-Lys-NH2), did not preserve the response to any tachykinin agonist. Protection of NK-1, NK-2 and NK-3 receptors preserved fully the responses to the preferential endogenous agonists, substance P, NKA and NKB, respectively, but they also preserved in part (30-40%) the responses to the nonpreferential agonists. Because substance P and NKA are coreleased from the same precursor in intestinal muscle tissue, the pattern implied the existence of considerable spareness in the contractile response of muscle cells to tachykinins. Studies on dispersed circular muscle cells using selective tachykinin agonists as protective agents confirmed the presence of three tachykinin receptor types. The results demonstrate the coexistence of NK-1, NK-2b and NK-3 receptors on muscle cells of rat intestine that are preferentially activated by substance P, NKA and NKB, respectively, and are coupled separately to one signaling pathway mediating contraction.