Shimizu T, Yoshitomi K, Nakamura M, Imai M
Shionogi Research Laboratories, Shinogi & Company, Osaka, Japan.
Am J Physiol. 1990 Sep;259(3 Pt 2):F408-14. doi: 10.1152/ajprenal.1990.259.3.F408.
Distal nephron segments are heterogenous with respect to adenylate cyclase responses to stimulation with parathyroid hormone (PTH) or calcitonin (CT). We examined effects of these hormones and of 8-(p-chlorophenylthio)-adenosine 3',5'-cyclic monophosphate (CPTcAMP) on net Ca absorption (Jnet Ca2+, pmol.min-1.mm-1) in rabbit distal nephron segments by in vitro microperfusion technique. We studied three segments, including distal convoluted tubule (DCT), connecting tubule (CNT), and cortical collecting duct (CCD). PTH (1 nM) in bath significantly increased Jnet Ca2+ from 2.28 +/- 0.35 to 9.44 +/- 1.13 in CNT, but did not affect Jnet Ca2+ in DCT or CCD. CT (1 nM) in bath significantly increased Jnet Ca2+ from 1.58 +/- 0.29 to 4.45 +/- 1.01 in DCT, whereas it did not affect Jnet Ca2+ either in CNT or in CCD. CPTcAMP (30 microM) in bath significantly increased Jnet Ca2+ from 2.29 +/- 0.42 to 3.97 +/- 0.43 in DCT and from 2.43 +/- 0.18 to 5.83 +/- 0.37 in CNT, but it did not affect Jnet Ca2+ in CCD. When Na+ was removed from bathing fluid or when 0.1 mM ouabain was added to bath, Jnet Ca2+ in both DCT and CNT significantly decreased. Furthermore, stimulatory effects of PTH and CT on Ca2+ absorption in the respective segments were abolished under these conditions. These results suggest that PTH and CT increase Ca2+ absorption in CNT and DCT, respectively, through cAMP-mediated mechanisms. Presence of a basolateral Na(+)-Ca2+ exchange process seems to be a prerequisite for effects of these hormones. However, exact intracellular mechanisms remain uncertain.
远曲小管各节段对甲状旁腺激素(PTH)或降钙素(CT)刺激的腺苷酸环化酶反应存在异质性。我们通过体外微灌注技术研究了这些激素以及8 - (对氯苯硫基) - 腺苷3',5' - 环磷酸(CPTcAMP)对兔远曲小管各节段净钙吸收(Jnet Ca2 +,pmol·min-1·mm-1)的影响。我们研究了三个节段,包括远曲小管(DCT)、连接小管(CNT)和皮质集合管(CCD)。浴槽中加入1 nM的PTH可使CNT中的Jnet Ca2 +从2.28±0.35显著增加至9.44±1.13,但对DCT或CCD中的Jnet Ca2 +无影响。浴槽中加入1 nM的CT可使DCT中的Jnet Ca2 +从1.58±0.29显著增加至4.45±1.01,而对CNT或CCD中的Jnet Ca2 +均无影响。浴槽中加入30 μM的CPTcAMP可使DCT中的Jnet Ca2 +从2.29±0.42显著增加至3.97±0.43,使CNT中的Jnet Ca2 +从2.43±0.18显著增加至5.83±0.37,但对CCD中的Jnet Ca2 +无影响。当从浴液中去除Na +或向浴槽中加入0.1 mM哇巴因时,DCT和CNT中的Jnet Ca2 +均显著降低。此外,在这些条件下,PTH和CT对各节段钙吸收的刺激作用均被消除。这些结果表明,PTH和CT分别通过cAMP介导的机制增加CNT和DCT中的钙吸收。基底外侧Na( + ) - Ca2 +交换过程的存在似乎是这些激素发挥作用的前提条件。然而,确切的细胞内机制仍不确定。