Mechanisms and Importance of Opioid and ORL-1 Receptor Coupling to Ca2+ Channel Subtypes 1. What are the molecular identities of opioid and orphanin FQ-sensitive Ca2+ channel subtypes? a. Do ORL- 1 receptors couple like opioid receptors to L-type Ca2+ channels when expressed in GH3 cells? b. Which different L-type Ca2+ channel a1 subunit transcripts are expressed by GH3 cells? c. Do antisense oligonucleotides to the a1 subunit abolish the opioid- and orphanin-sensitive Ca2+ current component? d. Do opioid and ORL-1 receptors expressed in HEK293 cells couple to Ca2+ channels formed by a10 subunits? 2. What G protein mechanisms couple opioid and ORL-1 receptors to CA2+ channels? a. Is there a consensus sequence at which bg binds to all opioid and orphanin FQ regulated Ca2+ channels? b. Does a peptide mimicking this sequence prevent receptor coupling to L- type Ca2+ channels in GH3 cells? c. Can a similar approach uncouple opioid receptors from a1a, a1b and a1d Ca2+ channels in HEK293 cells? 3. What is the contribution of L-type Ca2+ channels, relative to other effectors, in the modulation of vesicular release by opioids and orphanin FQ? a. Other than Ca2+ channels, what effectors are regulated by opioids and orphanin FQ in GH3 cells? b. Do opioids inhibit pro[actin release from GH3 cells through G protein bg subunits? c. What is the contribution of L-type Ca2+ channel inhibition in the opioid regulation of prolactin release from GH3 cells? 4. Do specific Ca2+ channel subtypes have a role in the central actions of opioids and orphanin FQ? a. Are a10 subunits (or other opioid and orphanin FQ sensitive subunits) coexpressed with opioid and/or ORL-1 receptors in central neurons? b. Do specific Ca2+ channel subtypes participate in the opioid and/or orphanin FQ regulation of dopamine release in the reward pathway?
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