Glucocorticoids isoforms

Recently, Tse et al. [73] and Orlowski et al. [74] have cloned a third isoform of Na /H exchanger (named NHE-3). The inferred 832-amino acid sequence of rabbit NHE-3 is 41% identical with NHE-1, 44% identical with NHE-2, and has a similar secondary structure. In contrast to NHE-1 and NHE-2, NHE-3 is only expressed in epithelia in intestine and kidney. Moreover, administration of glucocorticoids, which stimulates transport activity of the apical Na /H" exchanger in rabbit intestine, increased levels of NHE-3 transcripts but did not affect NHE-1 or NHE-2 [75]. Taken together, these results suggest that NHE-3 may encode a resistant-type Na /H exchanger of epithelia. A fourth Na /H exchanger isoform (NHE-4) is preferentially expressed in stomach [74]. 

Gougat, C., D. Jaffuel, R. Gagliardo, C. Henriquet, J. Bousquet, P. Demoly, and M. Mathieu. 2002. Overexpression of the human glucocorticoid receptor alpha and beta isoforms inhibits AP-1 and NF-kappaB activities hormone independently. J Mol Med 80(5) 309-18. 

Sousa AR, Lane SJ, Cidlowski JA, Staynov DZ, Lee TH. (2000) Glucocorticoid resistance in asthma is associated with elevated in vivo expression of the glucocorticoid receptor beta-isoform. J Allergy Clin Immunol. 105, 943-950. 

Mendel DB, Orti E. (1988) Isoform composition and stoichiometry of the approx 90-kDa heat shock protein associated with glucocorticoid receptors. J Biol Chem. 263, 6695-6702. 

Oakley RH, Sar M, Cidlowski JA. (1996) The human glucocorticoid receptor beta isoform. Expression, biochemical properties, and putative function. J Biol Chem. 271, 9550-9559. 

Table 2 Nuclear receptors (NR) for enzyme inducers. Enzyme inducers are now known to act as ligands to nuclear receptors, leading to gene activation and increased synthesis of the enzyme. Affinity of inducers to die receptors is now known to be responsible for the differential induction potential and can explain die observed species-differences in induction. The receptors tabulated are aryl hydrocarbon receptors (AhR), constituitively androstane receptor (CAR), pregnane X receptor (PXR), and glucocorticoid receptor (GR). The isoforms in bold type are the major isoform regulated by the corresponding receptors.

NITRERGIC STIMULANTS mimic, or cause the production and release of nitric oxide (NO), which is an important mediator that is synthesized on demand. The actions of nitric oxide are very widespread, and imbalance is likely to be involved in a number of disease states. Nitric oxide synthase (NOS) has a widespread distribution in the body, and isoforms are recognized specifically constitutive and inducible (iNOS) forms. Both forms are cytosolic, Ca /calmodulin and NADPH-dependent, and inhibited by L-arginine derivatives. Induction of iNOS is by various inflammatory cytokines, particularly those stimulated by bacterial lipopolysaccarides, including tumour necrosis factor a. interferon 7 and interleukin 1 p. Induction of iNOS only is inhibited by GLUCOCORTICOIDS. 

Lu NZ, Cidlowski JA Translational regulatory mechanisms generate N-terminal glucocorticoid receptor isoforms with unique transcriptional target genes. Mol Cell 2005 18 331-342. 

Lu NZ, Cidlowski JA The origins and functions of multiple human glucocorticoid receptor isoforms. Ann NY Acad Sci 2004 1024 102-123. 

---