Differential in vivo internalization of MOR-1 and MOR-1C by morphine

Neuroreport. 2001 Oct 8;12(14):3069-72. doi: 10.1097/00001756-200110080-00017.

Abstract

The mu opioid receptor MOR-1 is internalized by many mu agonists, but not morphine. To see whether differences in the intracellular carboxy terminus influences internalization, we examined internalization of a splice variant of the mu opioid receptor, MOR-1C, in the lateral septum of the mouse in vivo. Following intracerebroventricular (i.c.v.) saline treatment, MOR-1C-like immunoreactivity (LI) within neurons in naive mice was found predominantly in clusters close to the plasma membrane. Following either intracerebroventricular [d-Ala2, MePhe4,Gly(ol)5]enkephalin (DAMGO) or morphine, MOR-1C-LI clustered into endosomes in the cytoplasm. This effect was suppressed by prior administration of the opioid antagonist naloxone. In contrast, only DAMGO, and not morphine, internalized MOR-1-LI. These results illustrate differences in internalization between two MOR-1 variants that have alternative splicing at the COOH terminus.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Alternative Splicing / drug effects
  • Alternative Splicing / physiology*
  • Animals
  • Endocytosis / drug effects
  • Endocytosis / physiology*
  • Enkephalin, Ala(2)-MePhe(4)-Gly(5)- / pharmacology
  • Immunohistochemistry
  • Male
  • Mice
  • Morphine / pharmacology*
  • Naloxone / pharmacology
  • Neurons / cytology
  • Neurons / drug effects
  • Neurons / metabolism*
  • Protein Isoforms / drug effects
  • Protein Isoforms / genetics
  • Protein Isoforms / metabolism
  • Protein Structure, Tertiary / genetics
  • Protein Transport / drug effects
  • Protein Transport / physiology*
  • Receptors, Opioid, mu / drug effects
  • Receptors, Opioid, mu / genetics*
  • Receptors, Opioid, mu / metabolism
  • Septal Nuclei / cytology
  • Septal Nuclei / drug effects
  • Septal Nuclei / metabolism*

Substances

  • Protein Isoforms
  • Receptors, Opioid, mu
  • Enkephalin, Ala(2)-MePhe(4)-Gly(5)-
  • Naloxone
  • Morphine