title: Receptor crosstalk protein, calcyon, regulates affinity state of dopamine D1 receptors.
abstract: The recently cloned protein, calcyon, potentiates crosstalk between G(s)-coupled dopamine D1 receptors and heterologous G(q/11)-coupled receptors allowing dopamine D1 receptors to stimulate intracellular Ca(2+) release, in addition to cAMP production. This crosstalk also requires the participating G(q/11)-coupled receptors to be primed by their agonists. We examined the ability of calcyon and priming to regulate the affinity of dopamine D1 receptors for its ligands. Receptor binding assays were performed on HEK293 cell membrane preparations expressing dopamine D1 receptors either alone or in combination with calcyon. Co-expression of dopamine D1 receptor and calcyon affected neither the affinity of this receptor for antagonists nor the affinity of agonist binding to this receptor high and low-affinity states. However, the presence of calcyon dramatically decreased the proportion of the high-affinity dopamine D1 receptor agonist binding sites. This decrease was reversed by carbachol, which primes the receptor crosstalk by stimulating endogenous G(q/11)-coupled muscarinic receptors. Our findings suggest that calcyon regulates the ability of dopamine D1 receptors to achieve the high-affinity state for agonists, in a manner that depends on priming of receptor crosstalk.
authors.affiliation: Department of Oral and Craniofacial Biological Sciences and Program in Neuroscience, University of Maryland, 5-A-12, HHH 666 W. Baltimore St., Baltimore, MD 21201, USA. mlidow@umaryland.edu
authors.forename: M S
authors.initials: MS
authors.lastname: Lidow
authors.forename: A
authors.initials: A
authors.lastname: Roberts
authors.forename: L
authors.initials: L
authors.lastname: Zhang
authors.forename: P O
authors.initials: PO
authors.lastname: Koh
authors.forename: N
authors.initials: N
authors.lastname: Lezcano
authors.forename: C
authors.initials: C
authors.lastname: Bergson
mesh_terms: D001058:Apomorphine / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology; D001552:Benzazepines / Q000378:metabolism / Q000494:pharmacology; D001667:Binding, Competitive / Q000187:drug effects; D002217:Carbachol / Q000494:pharmacology; D002460:Cell Line; D018491:Dopamine Agonists / Q000378:metabolism / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000378:metabolism / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006160:Guanosine Triphosphate / Q000494:pharmacology; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000502:physiology*; D011869:Radioligand Assay; D020239:Receptor Cross-Talk / Q000187:drug effects / Q000502:physiology*; D017447:Receptors, Dopamine D1 / Q000235:genetics / Q000378:metabolism*; D014316:Tritium
chemical_list: D001552:Benzazepines; D018491:Dopamine Agonists; D018492:Dopamine Antagonists; D008565:Membrane Proteins; D017447:Receptors, Dopamine D1; C405464:calcyon; D014316:Tritium; C009074:N-n-propylnorapomorphine; D006160:Guanosine Triphosphate; D002217:Carbachol; D001058:Apomorphine