Grundemar L
Department of Clinical Pharmacology, Lund University Hospital, Sweden.
Regul Pept. 1998 Sep 25;75-76:181-4. doi: 10.1016/s0167-0115(98)00066-4.
The aim of the study was to examine which neuropeptide Y (NPY) receptor types that are coupled to inhibition of sensory C fiber-mediated contractions of the guinea pig bronchi. NPY and PYY evoked a concentration-dependent inhibition of the electrically stimulated contractions. The Y1 receptor-selective antagonist BIBP3226 (1 microM) evoked a rightward shift of the NPY-induced response. Also the Y1 (and Y4-Y6) receptor agonist [Leu31,Pro34]NPY suppressed the stimulated contractions with a potency similar to the parent molecule. BIBP3226 (1 microM) also attenuated the response induced by [Leu31,Pro34]NPY. The Y2 receptor agonist [Cys2, Aoc524, D-Cys27]NPY suppressed the stimulated contractions at 1 microM only. NPY 2-36 was much less potent than NPY itself and pretreatment with BIBP3226 did not affect the inhibitory response. Human pancreatic polypeptide (Y4-Y6 receptor agonist) was inactive (< or = 1 microM). In conclusion, NPY is capable of suppressing sensory nerve-mediated contractions in the guinea pig bronchi mainly via Y1 receptors.
本研究的目的是检测豚鼠支气管中与抑制感觉C纤维介导的收缩相关的神经肽Y(NPY)受体类型。NPY和PYY引起电刺激收缩的浓度依赖性抑制。Y1受体选择性拮抗剂BIBP3226(1微摩尔)使NPY诱导的反应向右移位。同样,Y1(以及Y4 - Y6)受体激动剂[Leu31,Pro34]NPY抑制刺激的收缩,其效力与母体分子相似。BIBP3226(1微摩尔)也减弱了[Leu31,Pro34]NPY诱导的反应。Y2受体激动剂[Cys2,Aoc524,D - Cys27]NPY仅在1微摩尔时抑制刺激的收缩。NPY 2 - 36的效力远低于NPY本身,用BIBP3226预处理不影响抑制反应。人胰多肽(Y4 - Y6受体激动剂)无活性(≤1微摩尔)。总之,NPY能够主要通过Y1受体抑制豚鼠支气管中感觉神经介导的收缩。