Cellular distribution and fate of the bradykinin antagonist HOE 140 in the rat kidney. Colocalization with the bradykinin B2 receptor.
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Biomedical subjects
Publications and source records attributed to V Velarde.
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The mature, fully differentiated connecting tubule (CNT) cell plays an important role in the regulation of serum potassium levels and synthesizes the enzyme tissue kallikrein, a main component of a renal vasoactive system, the kallikrein-kinin system. To characterize the growth of CNT cells (tissue kallikrein-producing cells), we studied the rat kidney at three different time points of postnatal development: at day 5, day 15, and day 30. The CNT cells were identified on tissue sections by a standardized immunohistochemical procedure. The tissue kallikrein content was determined by radioimmunoassay and the activity of the enzyme in kidney homogenates was measured using a selective synthetic substrate. The number of immunolabeled CNT and CNT cells per cortex area gradually increased from day 5 to day 30. A similar rise in the content and activity of tissue kallikrein was observed when the enzyme levels were determined by radioimmunoassay or by the enzymatic method. In addition, the morphometric analysis showed that the distal end of CNT had larger cells that displayed a more intense tissue kallikrein staining than those present in the proximal end, suggesting that the postnatal development of CNT is induced from its juxtamedullary portion. Our results show that tissue kallikrein expression is very low in the newborn rat, increasing gradually with age to reach adult levels at day 30. This finding, together with the morphometric data, suggests immaturity of CNT cells in newborn rats, a fact that could contribute to explaining the high serum potassium levels reported at this stage. In addition, the contrasting behavior of kallikrein and renin in the postnatal development (kallikrein increasing and renin decreasing) could explain the gradual decrease in renal vascular resistance and increase in renal blood flow observed after birth.
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G proteins play a central role in the mechanism of action of most hormones and neurotransmitters. They act as signal transducers between membrane receptors activated by extracellular stimuli on the one hand and intracellular effectors which control the concentrations of cytosolic messenger molecules (cAMP, cGMP, inositol phosphates, Ca2+) on the other. G proteins form a highly conserved family of membrane-associated proteins composed of alpha, beta and subunits. The alpha subunit, which is unique for each G protein, determines its biological activity and binds GDP and GTP. A number of diseases are already known to involve structural and/or quantitative changes of G proteins in plasma membranes. Interestingly, proteins encoded by some oncogenes show a high degree of homology with G proteins, which suggests that certain malignancies may be caused by alterations of transmembrane signaling.