Pharmacological characterization of inhibitory effects of postsynaptic opioid and cannabinoid receptors on calcium currents in neonatal rat nucleus tractus solitarius.
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.
Endoh
Takayuki
T
Department of Physiology, Tokyo Dental College, 1-2-2 Masago, Mihama-ku, Chiba 261-8502, Japan. tendoh@tdc.ac.jp
D000818:Animals; D000831:Animals, Newborn; D002118:Calcium / Q000502:physiology; D015220:Calcium Channels / Q000145:classification / Q000187:drug effects / Q000378:metabolism*; D020746:Calcium Channels, L-Type / Q000187:drug effects / Q000378:metabolism; D020865:Calcium Channels, P-Type / Q000187:drug effects / Q000378:metabolism; D020907:Calcium Channels, Q-Type / Q000187:drug effects / Q000378:metabolism; D063387:Cannabinoid Receptor Antagonists; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)- / Q000494:pharmacology; D007700:Kinetics; D009292:Narcotic Antagonists; D018847:Opioid Peptides / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D051381:Rats; D017208:Rats, Wistar; D043882:Receptors, Cannabinoid / Q000187:drug effects / Q000235:genetics; D011957:Receptors, Opioid / Q000819:agonists* / Q000187:drug effects / Q000235:genetics; D017473:Receptors, Opioid, kappa / Q000819:agonists / Q000037:antagonists & inhibitors / Q000187:drug effects; D017450:Receptors, Opioid, mu / Q000819:agonists / Q000037:antagonists & inhibitors / Q000187:drug effects; D017552:Solitary Nucleus / Q000166:cytology / Q000378:metabolism*; D000097629:Nociceptin
D002118:Calcium; D015220:Calcium Channels; D020746:Calcium Channels, L-Type; D020865:Calcium Channels, P-Type; D020907:Calcium Channels, Q-Type; D063387:Cannabinoid Receptor Antagonists; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D009292:Narcotic Antagonists; D018847:Opioid Peptides; D043882:Receptors, Cannabinoid; D011957:Receptors, Opioid; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; D000097629:Nociceptin