Ambudkar I S, Kuyatt B L, Roth G S, Baum B J
Clinical Investigations and Patient Care Branch, National Institute of Dental Research, Bethesda, MD 20892.
Mech Ageing Dev. 1988 Apr;43(1):45-60. doi: 10.1016/0047-6374(88)90096-6.
Previous experiments have shown that senescent rat parotid acinar cells display marked reductions in Ca2+ release following alpha 1-adrenoreceptor stimulation. We report here, that in this naturally occurring perturbation of exocrine secretion, ATP-dependent Ca2+ transport in the parotid basolateral plasma membrane, the principal Ca2+ extrusion pathway in the parotid, is also modified. ATP-dependent Ca2+ transport in membrane vesicles isolated from senescent rats (approx. 24 months) is decreased approximately 30-50% as compared to that in vesicles isolated from younger rats (approx. 4 months). This alteration in Ca2+ pump activity is not due to (i) non-specific effects of vesicle preparation in the two animal groups, (ii) increased leakiness to Ca2+, or (iii) any apparent alteration in permeability of the membrane to K+ and Cl-. Kinetic studies demonstrate that the ATP-dependent Ca2+ transport activity in vesicles from senescent rats has similar maximal velocity to that of vesicles from young adult rats (27 vs. 31 nmol Ca2+/mg protein per min), however, it exhibits an approximately 50% increase in Km for Ca2+ (91 nM vs. 60 nM). Cytosolic free Ca2+, measured by Quin 2 fluorescence, in parotid acini following alpha 1-adrenoreceptor stimulation was much less elevated in preparations from senescent rats. These results may account, at least in part, for the previously reported physiological alteration in Ca2+ efflux seen in senescent rat parotid cells.
先前的实验表明，衰老的大鼠腮腺腺泡细胞在α1-肾上腺素能受体刺激后，Ca2+释放显著减少。我们在此报告，在这种外分泌的自然扰动中，腮腺基底外侧质膜中依赖ATP的Ca2+转运（腮腺中主要的Ca2+外排途径）也发生了改变。与从年轻大鼠（约4个月）分离的膜囊泡相比，从衰老大鼠（约24个月）分离的膜囊泡中依赖ATP的Ca2+转运减少了约30 - 50%。Ca2+泵活性的这种改变并非由于：（i）两组动物中膜囊泡制备的非特异性影响；（ii）对Ca2+的渗漏增加；或（iii）膜对K+和Cl-的通透性有任何明显改变。动力学研究表明，衰老大鼠膜囊泡中依赖ATP的Ca2+转运活性与年轻成年大鼠膜囊泡的最大速度相似（分别为每分钟每毫克蛋白27和31 nmol Ca2+），然而，其对Ca2+的Km增加了约50%（分别为91 nM和60 nM）。用Quin 2荧光法测量，α1-肾上腺素能受体刺激后衰老大鼠腮腺腺泡中的胞质游离Ca2+升高幅度小得多。这些结果可能至少部分解释了先前报道的衰老大鼠腮腺细胞中Ca2+外流的生理改变。
