Bishai John M, Penninga Luit, Nijland Roel, Meulenaar Rogier, Gheorghe Ciprian P, Zhao Yu, Buchholz John N, Zhang Lubo, Longo Lawrence D
Center for Perinatal Biology, Department of Physiology, Loma Linda University School of Medicine, Loma Linda, California 92350, USA.
Am J Physiol Regul Integr Comp Physiol. 2002 Jun;282(6):R1654-62. doi: 10.1152/ajpregu.00475.2001.
In ovine cerebral arteries, adrenergic-mediated vasoconstrictor responses differ significantly with developmental age. We tested the hypothesis that, in part, these differences are a consequence of altered alpha(2)-adrenergic receptor (alpha(2)-AR) density and/or affinity. In fetal (approximately 140 days) and adult sheep, we measured alpha(2)-AR density and affinity with the antagonist [(3)H]idazoxan in main branch cerebral arteries and other vessels. We also quantified contractile responses in middle cerebral artery (MCA) to norepinephrine (NE) or phenylephrine in the presence of the alpha(2)-AR antagonists yohimbine and idazoxan and contractile responses to the alpha(2)-AR agonists clonidine and UK-14304. In fetal and adult cerebral artery homogenates, alpha(2)-AR density was 201 +/- 18 and 52 +/- 6 fmol/mg protein, respectively (P < 0.01); however, antagonist affinity values did not differ. In fetal, but not adult, MCA, 10(-7) M yohimbine significantly decreased the pD(2) for NE-induced tension in the presence of 3 x 10(-5) M cocaine, 10(-5) M deoxycorticosterone, and 10(-6) M tetrodotoxin. In fetal, but not adult, MCA, UK-14304 induced a significant decrease in pD(2) for the phenylephrine dose-response relation. In addition, stimulation-evoked fractional NE release was significantly greater in fetal than in adult cerebral arteries. In the presence of 10(-6) M idazoxan to block alpha(2)-AR-mediated inhibition of prejunctional NE release, the fractional NE release was significantly increased in both age groups. We conclude that in fetal and adult ovine cerebral arteries, alpha(2)-AR appear to be chiefly prejunctional. Nonetheless, the fetal cerebral arteries appear to have a significant component of postjunctional alpha(2)-AR.
在绵羊脑动脉中，肾上腺素能介导的血管收缩反应随发育年龄的变化而有显著差异。我们检验了这样一个假说，即这些差异部分是由于α₂-肾上腺素能受体（α₂-AR）密度和/或亲和力改变所致。在胎儿（约140天）和成年绵羊中，我们用拮抗剂[³H]咪唑克生测量了脑动脉主要分支和其他血管中α₂-AR的密度和亲和力。我们还在存在α₂-AR拮抗剂育亨宾和咪唑克生的情况下，定量了大脑中动脉（MCA）对去甲肾上腺素（NE）或苯肾上腺素的收缩反应，以及对α₂-AR激动剂可乐定和UK-14304的收缩反应。在胎儿和成年脑动脉匀浆中，α₂-AR密度分别为201±18和52±6 fmol/mg蛋白（P<0.01）；然而，拮抗剂亲和力值并无差异。在胎儿而非成年的MCA中，10⁻⁷ M育亨宾在存在3×10⁻⁵ M可卡因、10⁻⁵ M脱氧皮质酮和10⁻⁶ M河豚毒素的情况下，显著降低了NE诱导张力的pD₂值。在胎儿而非成年的MCA中，UK-14304使苯肾上腺素剂量反应关系的pD₂值显著降低。此外，刺激诱发的NE分数释放量在胎儿脑动脉中显著高于成年脑动脉。在存在10⁻⁶ M咪唑克生来阻断α₂-AR介导的对节前NE释放的抑制作用时，两个年龄组的NE分数释放量均显著增加。我们得出结论，在胎儿和成年绵羊脑动脉中，α₂-AR似乎主要位于节前。尽管如此，胎儿脑动脉似乎有相当一部分α₂-AR位于节后。
