Opioid receptor modulation by cannabinoids and receptor expression in culture

Date

1990

Authors

Vaysse, Pierre Jean-Jacques

Journal Title

Journal ISSN

Volume Title

Publisher

ProQuest Dissertations & Theses

YU Faculty Profile

Abstract

The existence of specific binding sites for opiate alkaloids in mammalian central nervous system was first reported more than 15 years ago. It is now generally accepted that the brain contains at least three distinct opioid receptor types, referred to as {dollar}\mu{dollar}, {dollar}\delta{dollar}, and {dollar}\kappa{dollar} opioid receptors.;We have investigated the influence of cannabinoids on opioid receptors of rat neuronal membranes. Treatment of membrane with {dollar}\Delta\sp9{dollar}-tetrahydrocannabinol decreased, in a noncompetitive manner, specific in vitro binding of {dollar}\mu{dollar} and {dollar}\delta{dollar} opioid ligands but not {dollar}\kappa{dollar} ligands. These results indicate that cannabinoids, at a relatively low dose, modulate {dollar}\mu{dollar} and {dollar}\delta{dollar} opioid receptor proteins.;As cell culture is a useful system for the study of receptor proteins, we have used this method to characterize the different opioid receptors. Specific binding of {dollar}\mu{dollar} opioid ligands to homogenates of cultured striatal neurons was stereospecific, saturable and of high affinity. {dollar}\delta{dollar} receptors were undetectable and {dollar}\kappa{dollar} receptors were found not to exceed 20% of total opioid receptors. These data demonstrate the predominance of {dollar}\mu{dollar} opioid receptors in cultures of embryonic rat striatum.;We then studied the expression of preproenkephalin and preprodynorphin mRNA by developing glia and neurons. The level of preproenkephalin mRNA in cultured astrocytes derived from different areas of the brain was comparable to levels present in cultured embryonic neurons. By contrast, although cultured hypothalamic neurons contained substantial levels of preprodynorphin mRNA, levels of this mRNA were not detectable in cultured astrocytes from any brain region or in cultured striatal neurons.;Together, these observations suggest the feasibility of using primary cell cultures to study the expression of opioid receptors and opioid peptides.

Description

Keywords

Neurosciences.

Citation

Source: Dissertation Abstracts International, Volume: 51-12, Section: B, page: 5741.;Advisors: R. Suzanne Zukin.