delta-Opioid receptors are more efficiently coupled to adenylyl cyclase than to L-type Ca(2+) channels in transfected rat pituitary cells

P L Prather, L Song, E T Piros, P Y Law, T G Hales

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22 Citations (Scopus)


Opioid receptors often couple to multiple effectors within the same cell. To examine potential mechanisms that contribute to the specificity by which delta-receptors couple to distinct intracellular effectors, we stably transfected rat pituitary GH(3) cells with cDNAs encoding for delta-opioid receptors. In cells transfected with a relatively low delta-receptor density of 0.55 pmol/mg of protein (GH(3)DOR), activation of delta-receptors produced inhibition of adenylyl cyclase activity but was unable to alter L-type Ca(2+) current. In contrast, activation of delta-receptors in a clone that contained a higher density of delta-receptors (2.45 pmol/mg of protein) and was also coexpressed with mu-opioid receptors (GH(3)MORDOR), resulted in not only the expected inhibition of adenylyl cyclase activity but also produced inhibition of L-type Ca(2+) current. The purpose of the present study was to determine whether these observations resulted from differences in delta-opioid receptor density between clones or interaction between delta- and mu-opioid receptors to allow the activation of different G proteins and signaling to Ca(2+) channels. Using the delta-opioid receptor alkylating agent SUPERFIT, reduction of available delta-opioid receptors in GH(3)MORDOR cells to a density similar to that of delta-opioid receptors in the GH(3)DOR clone resulted in abolishment of coupling to Ca(2+) channels, but not to adenylyl cyclase. Furthermore, although significantly greater amounts of all G proteins were activated by delta-opioid receptors in GH(3)MORDOR cells, delta-opioid receptor activation in GH(3)DOR cells resulted in coupling to the identical pattern of G proteins seen in GH(3)MORDOR cells. These findings suggest that different threshold densities of delta-opioid receptors are required to activate critical amounts of G proteins needed to produce coupling to specific effectors and that delta-opioid receptors couple more efficiently to adenylyl cyclase than to L-type Ca(2+) channels.

Original languageEnglish
Pages (from-to)552-62
Number of pages11
JournalJournal of Pharmacology and Experimental Therapeutics
Issue number2
Publication statusPublished - Nov 2000


  • Adenylate Cyclase Toxin
  • Adenylyl Cyclase Inhibitors
  • Adenylyl Cyclases/metabolism
  • Alkylating Agents/pharmacology
  • Analgesics, Opioid/pharmacology
  • Animals
  • Barium/metabolism
  • Calcium Channels, L-Type/metabolism
  • Enkephalin, D-Penicillamine (2,5)-/pharmacology
  • Fentanyl/analogs & derivatives
  • Heterotrimeric GTP-Binding Proteins/biosynthesis
  • Ion Channels/physiology
  • Naltrexone/analogs & derivatives
  • Pituitary Gland/cytology
  • Rats
  • Receptors, Opioid, delta/genetics
  • Receptors, Opioid, mu/genetics
  • Transfection
  • Virulence Factors, Bordetella/pharmacology


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