Nuclear pharmacological effects

Today, we realize that drug binding/receptor sites that produce pharmacological effects may be part of any cellular constituent for example, nuclear DNA, mitochondrial enzymes, ribosomal RNA, cytosolic components, and cell membranes and wall, to name the most obvious. Nevertheless, in contemporary pharmacology, some authors and researchers apply a more restricted use of the term receptor, reserving it for protein complexes embedded in, and spanning, cellular membranes. However, exceptions to this classification system clearly exist. For example, steroids are known to interact with cytosolic receptors that transport them into the nucleus (their site of... 

Many clinically relevant NSAIDs exert off-target effects unrelated to their ability to inhibit COX enzymes. For example, INDO and SS induce apoptosis of tumor cells and modulate y-secretase activity (15, 16). INDO also activates the nuclear transcription factor PPARy (17). The complexity of in vivo pharmacologic effects makes it a challenge to separate the contribution of COX inhibition from other effects in a given pharmacologic response. Thus, the removal of COX inhibitory activity by a minor modification, such as the removal of a methyl group, provides an opportunity to dissect COX-dependent and COX-independent effects of certain NSAIDs. In fact, DM-INDO and DM-SS activate PPARy in HCA-7 cells with dose responses similar to those of the parent drugs (14). Likewise, the rfei -methyl compounds exhibit potency similar to the parent compounds in their ability to induce apoptosis in RKO cells, a human colon cancer cell line, and to activate PPARy in cellular reporter assays. 

The corticosteroids exert their pharmacological effect by modifying RNA and protein synthesis in target tissue. After binding to the specific cytoplasmic protein receptors, the steroid-receptor complex is transported to the nucleus, where it binds to the nuclear chromatin, thereby altering the transcription of RNA. Since the steroids are not stored, the steroid concentration in the plasma is maintained by regulation of steroid biosynthesis. 

Nuclear Medicine uses radioactive compounds for in vivo imaging and therapeutic purposes. Such compounds, named radiopharmaceuticals, are used in very low concentration (10 -10 M), having no pharmacological effect. Depending on the infiinsic physical characteristics of the radionuclide, the radiopharmaceuticals are used for in vivo imaging or targeted radionuclide therapy (TRT). 

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