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Inositol phosphates and intracellular calcium after bradykinin stimulation in fibroblasts from young, normal aged and Alzheimer donors

1991; Elsevier BV; Volume: 12; Issue: 5 Linguagem: Inglês

10.1016/0197-4580(91)90075-u

1558-1497

H. M. Huang, Lourdes Toral‐Barza, Howard T. Thaler, B. Tofel-Grehl, Gary E. Gibson,

Coagulation, Bradykinin, Polyphosphates, and Angioedema

Several studies suggest that alterations in the receptor-mediated phosphoinositide cascade and cytosolic free calcium concentration ([Ca2+]i) are involved in the pathophysiology of aging and Alzheimer's disease. Therefore, the phosphoinositide cascade and [Ca2+]i were determined under resting conditions and after stimulation with bradykinin (100 nM) in cultured human skin fibroblasts from young (21±3 years), normal aged (59±6 years) and Alzheimer subjects (58±6 years). The inositol polyphosphates (IP3, IP2 and IP) were monitored after prelabeling the cells with [3H]inositol in serum free medium. [Ca2+]i was determined with the fluorescent probe, fura-2AM, under exactly analogous conditions. The bradykinin-induced formation of IP3 and IP2 increased significantly in fibroblasts from normal aged and Alzheimer donors compared to young subjects, but did not differ from each other. Bradykinin-induced IP3 formation was 63–117% above the young group at time points between 10–60 s in normal aged or Alzheimer donors. Bradykinin-induced IP2 formation was 49–59% above the young group at time points between 10–60 s in normal aged or Alzheimer subjects. Neither the basal [Ca2+]i, nor the bradykinin-stimulated [Ca2+]i, differed among fibroblasts from young, normal aged and Alzheimer donors. The precise molecular basis and pathophysiological significance of the enhanced bradykinin-induced phosphoinositide cascade in fibroblasts from aged donors remains to be determined.