Prieto D, Buus C L, Mulvany M J, Nilsson H
Departamento de Fisiología, Facultad de Veterinaria, Universidad Complutense, 28040-Madrid, Spain.
Br J Pharmacol. 2000 Apr;129(8):1689-99. doi: 10.1038/sj.bjp.0703256.
Simultaneous measurements of intracellular calcium concentration (Ca(2+)) and tension were performed to clarify whether the mechanisms which cause the neuropeptide Y (NPY)-elicited contraction and potentiation of noradrenaline contractions, and the NPY inhibition of forskolin responses are linked to a single or different NPY receptor(s) in rat mesenteric small arteries. In resting arteries, NPY moderately elevated Ca(2+) and tension. These effects were antagonized by the selective Y(1) receptor antagonist, (R)-N(2)-(diphenacetyl)-N-[(4-hydroxyphenyl)methyl]-D-argininea mide (BIBP 3226) (apparent pK(B) values of 8.54+/-0.25 and 8.27+/-0.17, respectively). NPY (0.1 microM) caused a near 3 fold increase in sensitivity to noradrenaline but did not significantly modify the tension-Ca(2+) relationship for this agonist. BIBP 3226 competitively antagonized the contractile response to NPY in arteries submaximally preconstricted with noradrenaline (pA(2) 7.87+/-0.20). In arteries activated by vasopressin, the adenylyl cyclase activator forskolin (3 microM) induced a maximum relaxation and a return of Ca(2+) to resting levels. NPY completely inhibited these effects. The contractile responses to NPY in arteries maximally relaxed with either sodium nitroprusside (SNP) or nifedipine were not significantly higher than those evoked by the peptide at resting tension, in contrast to the contractions to NPY in forskolin-relaxed arteries. BIBP 3226 competitively antagonized the contraction to NPY in forskolin-relaxed arteries with a pA(2) of 7.92+/-0.29. Electrical field stimulation (EFS) at 8-32 Hz caused large contractions in arteries relaxed with either forskolin or noradrenaline in the presence of phentolamine. These responses to EFS were inhibited by BIBP 3226. Similar EFS in resting, non-activated arteries did not produce any response. The present results suggest that different intracellular pathways are linked to a single NPY Y(1) receptor in intact rat mesenteric small arteries, and provide little support for involvement of other postjunctional NPY receptors in the contractile responses to NPY. Neurally released NPY also seems to act through Y(1) receptors, and may serve primarily as an inhibitor of vasodilatation.
同时测量细胞内钙浓度（Ca(2+)）和张力，以阐明导致神经肽Y（NPY）引起的收缩、去甲肾上腺素收缩增强以及NPY对福斯可林反应的抑制作用的机制是否与大鼠肠系膜小动脉中的单一或不同NPY受体相关。在静息动脉中，NPY适度升高Ca(2+)和张力。这些作用被选择性Y(1)受体拮抗剂（R）-N(2)-(二苯乙酰基)-N-[(4-羟基苯基)甲基]-D-精氨酸酰胺（BIBP 3226）拮抗（表观pK(B)值分别为8.54±0.25和8.27±0.17）。NPY（0.1 microM）使对去甲肾上腺素的敏感性增加近3倍，但未显著改变该激动剂的张力-Ca(2+)关系。BIBP 3226竞争性拮抗用去甲肾上腺素次最大预收缩的动脉中对NPY的收缩反应（pA(2) 7.87±0.20）。在由血管加压素激活的动脉中，腺苷酸环化酶激活剂福斯可林（3 microM）诱导最大舒张并使Ca(2+)恢复到静息水平。NPY完全抑制这些作用。与福斯可林舒张的动脉中对NPY的收缩相反，用硝普钠（SNP）或硝苯地平最大舒张的动脉中对NPY的收缩反应与静息张力下肽引起的反应相比无显著升高。BIBP 3226竞争性拮抗福斯可林舒张的动脉中对NPY的收缩，pA(2)为7.92±0.29。在酚妥拉明存在下，8 - 32 Hz的电场刺激（EFS）在福斯可林或去甲肾上腺素舒张的动脉中引起大的收缩。这些对EFS的反应被BIBP 3226抑制。在静息、未激活的动脉中类似的EFS未产生任何反应。目前的结果表明，在完整的大鼠肠系膜小动脉中，不同的细胞内途径与单一的NPY Y(1)受体相关，并且几乎没有证据支持其他接头后NPY受体参与对NPY的收缩反应。神经释放的NPY似乎也通过Y(1)受体起作用，并且可能主要作为血管舒张的抑制剂。
