The Temozolomide Pitfall

1989). Thus, expression of UT receptor exclusively in the deeper inner medullary portions of the collecting duct in the embryonic metanephros is associated with epithelia undergoing functional differentiation and maturation. In contrast to the highly specific localization of UT in the young SD rat kidney, we have shown that UII immunoreactivity, although differing in immunostaining intensity, is present in a diffuse pattern throughout the metanephros and the postnatal kidney. The abundant cross-reactivity with UII antibody seen during renal development and maturation supports the notion that the kidney is a major source of urotensin Temozolomide peptide in mammals (Matsushita et al. 2001). The intensity of UII immunoreactivity correlates with UII mRNA levels, with distinct expression at E19, decreasing by birth, then increasing to higher levels by PN10. However, the additional increase in UII check details immunoreactivity between PN10 and PN28 is not reflected by a similar increase in UII mRNA. It is important to note that the UII primary antibody used herein was raised against the cyclic portion of the peptide; therefore, owing to the high degree of similarity between UII and URP (Sugo et al. 2003), it may detect either of the mature peptides, peptide fragments or prohormones (Winter et al. 1999; Song et al. 2006). The apparent mismatch between UII immunoreactivity and UII mRNA could therefore be explained by the cross-reactivity of the UII primary antibody with URP. Finally, it is notable that there was no significant difference in UII, URP or UT mRNA expression levels between medulla and cortex of 4-week-old animals, which contrasts with our previous report of elevated Moroxydine expression of UII, URP and UT mRNA in the adult SD rat medulla compared with the cortex (Song et al. 2006; Abdel-Razik et al. 2008). It is acknowledged that without confirming the RNA integrity, the validity of this mRNA relative quantification cannot be assured. However, taken together, the immunohistochemistry and mRNA data suggest that the UII system has not developed fully by 4 weeks of age. The notion that the UII system has not reached maturity by 4 weeks is supported by the in vivo assessment of renal function. Infusion of either exogenous rUII or rURP failed to elicit a renal response in the immature rat when compared with vehicle-infused animals. This lack of response contrasts with the marked antidiuresis and antinatriuresis associated with the infusion of rUII at 6 pmol min?1 (100 g body weight)?1 in the adult SD rat (Abdel-Razik et al. 2008). Indeed, using a similar experimental protocol, we have reported reductions in GFR, ERBF, urine flow and sodium excretion rates of 50% in response to a 6 pmol dose of rUII. At 4 weeks of age, urine concentrating ability is not developed fully in the rat, in part due to the immaturity of the loops of Henle.