Inverse agonists and neutral antagonists of alpha-1d adrenoceptor

• Published in: Journal of Pharmacological Sciences Vol. 91; no. suppl.2; p. 239
• Main Authors: Zhang Li, Tanaka Takashi, Israilova Malika, Suzuki Fumiko, Muramatsu Ikunobu
• Format: Journal Article
• Language: Japanese
• Published: The Japanese Pharmacological Society 2003
• ISSN: 1347-8613; 1347-8648

Alpha-1 adrenoceptors (ARs) are members of the G protein-coupled receptors and play critical roles in the regulation of a variety of physiological processes. Recently, recombinant alpha-id subtype was shown to have a relatively high constitutive activity in the absence of agonist. In the present study, we examined the effects of various drugs on the constitutive activity. At first, CHO cells expressed alpha-1d AR was treated for 72 hours with 22 drugs and the effects on receptor density was examined. The most drugs including BMY7378, tamsulosin and WB4101 produced a significant increase in alpha-1d AR. However, HEAT and prazosin failed to change the density and inhibited the upregulation induced by BMY7378. Basal production of inositol phosphates was reduced by BMY7378 and other drugs in CHO cells expressed alpha- 1d AR but in mock cells. However, HEAT and prazosin inhibited the effect of BMY7378 on inositol phosphate production without affecting the basal production. These results indicate that most drugs including BMY7378 are inverse agonists at alpha-1d AR, but that HEAT and prazosin behave like neutral antagonists, which have little effect on the constitutive activity.