Pharmacological characterization of inhibitory effects of postsynaptic opioid and cannabinoid receptors on calcium currents in neonatal rat nucleus tractus solitarius

Br J Pharmacol. 2006 Feb;147(4):391-401. doi: 10.1038/sj.bjp.0706623.

Abstract

1. The profile of opioid and cannabinoid receptors in neurons of the nucleus tractus solitarius (NTS) has been studied using the whole-cell configuration of the patch clamp technique. 2. Experiments with selective agonists and antagonists of opioid, ORL and cannabinoid receptors indicated that mu-opioid, kappa-opioid, ORL-1 and CB1, but not delta-opioid, receptors inhibit VDCCs in NTS. 3. Application of [D-Ala2, N-Me-Phe4, Gly5-ol]-enkephalin (DAMGO; mu-opioid receptor agonist), Orphanin FQ (ORL-1 receptor agonist) and WIN55,122 (CB1 receptor agonist) caused inhibition of I(Ba) in a concentration-dependent manner, with IC50's of 390 nM, 220 nM and 2.2 microM, respectively. 4. Intracellular dialysis of the G(i)-protein antibody attenuated DAMGO-, Orphanin FQ- and WIN55,122-induced inhibition of I(Ba). 5. Both pretreatment with adenylate cyclase inhibitor and intracellular dialysis of the protein kinase A (PKA) inhibitor attenuated WIN55,122-induced inhibition of I(Ba) but not DAMGO- and Orphanin FQ-induced inhibition. 6. Mainly N- and P/Q-type VDCCs were inhibited by both DAMGO and Orphanin FQ, while L-type VDCCs were inhibited by WIN55,122. 7. These results suggest that mu- and kappa-opioid receptors and ORL-1 receptor inhibit N- and P/Q-type VDCCs via G alpha(i)-protein betagamma subunits, whereas CB1 receptors inhibit L-type VDCCs via G alpha(i)-proteins involving PKA in NTS.

MeSH terms

  • Animals
  • Animals, Newborn
  • Calcium / physiology
  • Calcium Channels / classification
  • Calcium Channels / drug effects
  • Calcium Channels / metabolism*
  • Calcium Channels, L-Type / drug effects
  • Calcium Channels, L-Type / metabolism
  • Calcium Channels, P-Type / drug effects
  • Calcium Channels, P-Type / metabolism
  • Calcium Channels, Q-Type / drug effects
  • Calcium Channels, Q-Type / metabolism
  • Cannabinoid Receptor Antagonists*
  • Enkephalin, Ala(2)-MePhe(4)-Gly(5)- / pharmacology
  • Kinetics
  • Narcotic Antagonists*
  • Nociceptin
  • Opioid Peptides / pharmacology
  • Patch-Clamp Techniques
  • Rats
  • Rats, Wistar
  • Receptors, Cannabinoid / drug effects
  • Receptors, Cannabinoid / genetics
  • Receptors, Opioid / agonists*
  • Receptors, Opioid / drug effects
  • Receptors, Opioid / genetics
  • Receptors, Opioid, kappa / agonists
  • Receptors, Opioid, kappa / antagonists & inhibitors
  • Receptors, Opioid, kappa / drug effects
  • Receptors, Opioid, mu / agonists
  • Receptors, Opioid, mu / antagonists & inhibitors
  • Receptors, Opioid, mu / drug effects
  • Solitary Nucleus / cytology
  • Solitary Nucleus / metabolism*

Substances

  • Calcium Channels
  • Calcium Channels, L-Type
  • Calcium Channels, P-Type
  • Calcium Channels, Q-Type
  • Cannabinoid Receptor Antagonists
  • Narcotic Antagonists
  • Opioid Peptides
  • Receptors, Cannabinoid
  • Receptors, Opioid
  • Receptors, Opioid, kappa
  • Receptors, Opioid, mu
  • Enkephalin, Ala(2)-MePhe(4)-Gly(5)-
  • Calcium