Modin A, Malmström R E, Meister B
Department of Physiology, Karolinska Institute, Stockholm, SE-171 77, Sweden.
Neuropeptides. 1999 Aug;33(4):253-9. doi: 10.1054/npep.1999.0755.
Neuropeptide Y (NPY) -receptor subtypes were studied in the rat kidney in vivo by systemic administration of NPY, the two agonists [Leu(31), Pro(34)]NPY (Y1-receptor agonist) and NPY (13-36) (Y2-receptor agonist), or the Y1-receptor antagonist BIBP 3226. Effects on mean arterial blood pressure (MAP) and renal arterial blood flow were recorded. The Y1-receptor agonist evoked a dose-dependent increase in MAP concomitantly with a reduction in renal blood flow. At the largest dose administered (1.42 pmol/g), the Y1-agonist [Leu(31), Pro(34)] NPY increased MAP by 20 +/- 6 mmHg and reduced the renal vascular conductance by more than 50%. The same dose of the Y2-agonist NPY (13-36) did not evoke any clear-cut effects on the renal blood flow or MAP. Furthermore, administration of the Y1-receptor antagonist BIBP 3226 reduced the NPY-induced renal vasoconstriction, but did not affect the response to angiotensin II or phenylephrine. The effects evoked by 0.71 pmol/g NPY were almost abolished by 3 mg/kg BIBP 3226. In situ hybridization histochemistry was used to study the expression of Y1-receptor mRNA in the developing rat kidney. The levels of Y1-receptor mRNA expression in the vascular smooth muscle of the rat kidney varied at different ages, with low levels at postnatal day 10 and high levels at 20 days and again low levels at 40 days. In summary, the present study show a maturation-specific expression pattern of NPY Y1-receptor mRNA as well as functional effects of vascular NPY receptors of the Y1-subtype in the rat kidney.
通过对大鼠体内肾脏进行研究，系统给予神经肽Y（NPY）、两种激动剂[亮氨酸（31），脯氨酸（34）]NPY（Y1受体激动剂）和NPY（13 - 36）（Y2受体激动剂）或Y1受体拮抗剂BIBP 3226，对神经肽Y受体亚型进行了研究。记录了对平均动脉血压（MAP）和肾动脉血流量的影响。Y1受体激动剂引起MAP剂量依赖性增加，同时肾血流量减少。在给予的最大剂量（1.42 pmol/g）时，Y1激动剂[亮氨酸（31），脯氨酸（34）]NPY使MAP升高20±6 mmHg，并使肾血管传导率降低超过50%。相同剂量的Y2激动剂NPY（13 - 36）对肾血流量或MAP未产生任何明显影响。此外，给予Y1受体拮抗剂BIBP 3226可减轻NPY诱导的肾血管收缩，但不影响对血管紧张素II或去氧肾上腺素的反应。0.71 pmol/g NPY引起的效应几乎被3 mg/kg BIBP 3226消除。采用原位杂交组织化学方法研究了发育中大鼠肾脏Y1受体mRNA的表达。大鼠肾脏血管平滑肌中Y1受体mRNA表达水平在不同年龄有所变化，出生后第10天水平较低，20天时水平较高，40天时水平再次降低。总之，本研究显示了NPY Y1受体mRNA成熟特异性的表达模式以及大鼠肾脏中Y1亚型血管NPY受体的功能效应。
