Histamine H1 receptor (HRH1) (HRH1)

The Non-ER cytoplasmic tamoxifen-binding Site B, commonly referred to as Site B, is a low-affinity, high-capacity binding site for the drug tamoxifen and its metabolites, located primarily in the microsomal fraction of cells. Pharmacological research conducted in the 1980s and 1990s identified this site as the Histamine H1 receptor (HRH1), specifically an intracellular or microsomal form of the G protein-coupled receptor. Tamoxifen and its derivative Tesmilifene (DPPE) act as antagonists at this site, which is distinct from the primary estrogen receptor (ER) and the high-affinity microsomal antiestrogen binding site (AEBS, or Site A). Interaction with Site B is believed to mediate several non-genomic effects of tamoxifen, including the modulation of cell growth and the potentiation of cytotoxic chemotherapy. While the high-affinity Site A has been molecularly characterized as the EBP/DHCR7 enzyme complex, Site B remains a significant pharmacological target for understanding the multi-faceted actions of selective estrogen receptor modulators (SERMs) in cancer treatment.

Other names

Non-ER cytoplasmic tamoxifen-binding Site BLow-affinity antiestrogen binding siteSite BMicrosomal histamine receptorIntracellular histamine receptor

Antagonism of the histamine H1 receptor and inhibition of intracellular histamine signaling, which may modulate cell proliferation and enhance the efficacy of cytotoxic agents (Faye et al., 1983; Brandes et al., 1987).