Subdivision-specific responses of neurons in the nucleus of the tractus solitarius to activation of mu-opioid receptors in the rat.
Microinjection of opioid receptor agonists into the nucleus tractus solitarius (NTS) has differential effects on cardiovascular, respiratory, and gastrointestinal responses. This can be achieved either by presynaptic modulation of inputs onto neurons or by postsynaptic activation of receptors on neurons in specific regions. Therefore we sought to determine whether responses of neurons to activation of opioid receptors were dependent on their location within the NTS. Using whole cell patch-clamp recordings from neurons within the NTS, the mu opioid receptor (MOR) agonist [D-Ala(2), N-Me-Phe(4),Gly(5)-ol]-enkephalin (DAMGO, 100 nM) hyperpolarized a proportion of neurons in the medial, dorsomedial and dorsolateral NTS, whereas no postsynaptic responses were observed in remaining subdivisions. DAMGO reduced the amplitude of solitary tract-evoked excitatory postsynaptic potentials (EPSPs) in all neurons tested, regardless of subdivision. The kappa opioid receptor (KOR) agonist U69593 (10-20 microM) also hyperpolarized a small fraction of neurons (6/79) and decreased the amplitude of EPSPs in 50% of neurons. In contrast, the delta-opioid receptor agonist DPDPE (1-4 microM) had no presynaptic or postsynaptic effects on NTS neurons even after preincubation with bradykinin. Anatomical data at the light and electron microscopic level complemented electrophysiological observations with respect to MOR location and further showed that MORs were present at both presynaptic and postsynaptic sites in the dorsolateral NTS, often at the same synapse. These data demonstrate site specific responses of neurons to activation of MORs and KORs, which may underlie their ability to modulate different autonomic reflexes.
Poole
Sarah L
SL
Institute of Membrane and Systems Biology, Faculty of Biological Sciences, University of Leeds, Leeds LS2 9JT, UK.
Deuchars
Jim
J
Lewis
David I
DI
Deuchars
Susan A
SA
D000701:Analgesics, Opioid / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D004347:Drug Interactions; D004558:Electric Stimulation / Q000379:methods; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D066298:In Vitro Techniques; D008297:Male; D016253:Microscopy, Immunoelectron / Q000379:methods; D009474:Neurons / Q000502:physiology* / Q000648:ultrastructure; D018408:Patch-Clamp Techniques / Q000379:methods; D051381:Rats; D017208:Rats, Wistar; D017450:Receptors, Opioid, mu / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000648:ultrastructure; D017552:Solitary Nucleus / Q000166:cytology*; D013004:Somatostatin / Q000031:analogs & derivatives / Q000494:pharmacology
D000701:Analgesics, Opioid; D017450:Receptors, Opioid, mu; C049352:phenylalanyl-cyclo(cysteinyltyrosyl-tryptophyl-ornithyl-threonyl-penicillamine)threoninamide; D013004:Somatostatin