gand-gated (LGIC), voltage-sensitive calcium and potassium (VSCC, Kir), and ion-modulated (ASIC) subtypes, all of which have similar but very distinct structural motifs. Ion channels can also be modulated by temperature, e.g., vanilloid receptors (59). This latter family., TRPV, has now been reclassified as part of the transient receptor potential (TRP) ion channel family. The steroid receptor su-perfamily comprises glucocorticoid (GR), progesterone (PR), mineralocorticoid (MR), androgen (AR), thyroid hormone (TR), and vitamin D3 (VDR) receptors (60). Another diverse class of targets that mediates or modulates the effects of drugs are the intracellular receptors, which includes the cytochrome P450 (CYP) family, the SMAD family of tumor suppressors, the retinoic acid receptor (RXR, RAR) superfamilies (61), receptor-activated transcription factors (RAFTs), and signal transducers and activators of transcription (STATs). The latter encompass AP-1, NFkB, NF-AT, STAT-1, PPARs, the hormone responsive elements on DNA and RNA promoters, and ribozymes. The interferon, tumor necrosis factor (TNF), and receptor kinase families are grouped together in the cytokine receptor class because of similarities in their signal transduction mechanisms.
In addition to this multitude of receptor classes, further complexity in conceptualizing receptors as distinct, classifiable entities is exemplified by recent findings related to GPCRs. By implicit definition, these receptors produce their physiological effects by coupling through the G-protein family. However, there are several instances where ion channels can produce their effects by coupling through G-proteins and also examples where GPCRs can function independently of G-proteins (62). Similarly, HCN-1 and HCN-3, members of the hyperpo-larizing activated, cyclic nucleotide-regulated receptor family are insensitive to cyclic nucleotides. Receptor classification is thus a very dynamic process with few absolutes.
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