Cyclooxygenases in the Collecting Duct of Neonatal Rabbit Kidney

Abstract

COX 1 and 2 expression during the terminal phase of kidney development is poorly understood. To obtain information about this process we followed the primary appearance of cyclooxygenases in collecting duct (CD) epithelia of the neonatal rabbit kidney with immunohistochemical and two dimensional electrophoretical methods. In the fully embryonic cortical zone immunohistochemical expression of COX 1 is seen in all cells of the CD ampulla, while COX 2 is lacking within the nephron inducer. Within the matured cortical collecting duct (CCD) COX 1 and 2 immunoreactivity could not be detected. In contrast, a heterogeneous expression profile for COX 1 and 2 is found in the outer medullary CD (OMCD), since not all cells showed immunohistochemical labeling. Within the inner medullary CD (IMCD) nearly all cells express both cyclooxygenases. As revealed by western blot experiments generated embryonic CD epithelia in perfusion culture demonstrate high COX 1 presence at the begin of culture, while COX 2 is found to a minor degree. From day 3 until day 14 continuous levels of COX 1 and 2 expression are detected. Administration of 1 x 10^-7 mmol/l aldosterone does not influence COX expression, while application of 100 mmol/l NaCl increases COX 2 fourfold. The upregulation of COX 2 by a chronic NaCl load in embryonic epithelia suggests in part a constitutive and in part a facultative expression during CD cell differentiation.

Nimesulide, a Cyclooxygenase-2 Preferential Inhibitor, Impairs Renal Function in the Newborn Rabbit

“…In the adult kidney cortex, constitutive expression of COX2 is found mainly in the thick ascending limb of the loop of Henle (28), which is one of the main sites of water reabsorption. Schumacher et al (29) recently demonstrated on cryosections of neonatal rabbit kidneys that both COX1 and COX2 are constitutively expressed in the medullary collecting duct, without labeling the cortical collecting duct. This suggests a direct role of COX2 inhibition in the medullary collecting duct.…”

“…These discrepancies do not allow us to conclude definitely on the selectivity of nimesulide in our model. We therefore cannot totally exclude the possibility that the reduction of CH 2 O by nimesulide might also result from partial COX1 inhibition, as COX1 is widely expressed in the collecting duct (29).…”

“…The overall data therefore suggest a major role of both COX1 and COX2 isoforms-derived PGs in protecting the newborn kidney, which is perfused at low renal arterial pressure. Indeed, it has been demonstrated that the low renal expression of COX2 at birth increases rapidly in the first two postnatal weeks, before gradually declining to low levels in normal adult rats and rabbits (29,40). Likewise, newborn infants have high plasma levels of vasodilating PGs that modulate the highly activated vasoconstrictor state of the neonatal renal circulation (41).…”

Beneficial effect of insulin-like growth factor-1 on hypoxemic renal dysfunction in the newborn rabbit

“…We also previously demonstrated in the same model that the newborn's kidney is highly sensitive to cyclooxygenase 2 (COX2) inhibition and that PGs play a key role in the regulation of neonatal GFR [29], through a rapid increase of COX2 renal expression during the first two postnatal weeks [38,39]. Prostaglandin synthesis inhibition with indomethacin completely blocked the IGF-1-induced increase in GFR in vitro and in vivo [24,40,41].…”

Bridging the gap between traditional cell cultures and bioreactors applied in regenerative medicine: practical experiences with the MINUSHEET perfusion culture system

“…As a consequence, for special demands culture media have to be adapted by addition of defined electrolyte concentrations so that an adequate degree of differentiation is achieved (Schumacher et al , 2002b.…”