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

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. Experiments with selective agonists and antagonists of opioid, ORL and cannabinoid receptors indicated that μ ‐opioid, κ ‐opioid, ORL‐1 and CB1, but not δ ‐opioid, receptors inhibit VDCCs in NTS. Application of [ D ‐Ala 2 , N ‐Me‐Phe 4 , Gly 5 ‐ol]‐enkephalin (DAMGO; μ ‐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 IC 50 's of 390 n M , 220 n M and 2.2  μ M , respectively. Intracellular dialysis of the G i ‐protein antibody attenuated DAMGO‐, Orphanin FQ‐ and WIN55,122‐induced inhibition of I Ba . 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. Mainly N‐ and P/Q‐type VDCCs were inhibited by both DAMGO and Orphanin FQ, while L‐type VDCCs were inhibited by WIN55,122. These results suggest that μ ‐ and κ ‐opioid receptors and ORL‐1 receptor inhibit N‐ and P/Q‐type VDCCs via G α i ‐protein βγ subunits, whereas CB1 receptors inhibit L‐type VDCCs via G α i ‐proteins involving PKA in NTS.British Journal of Pharmacology (2006) 147 , 391–401. doi: 10.1038/sj.bjp.0706623