Effects of substance P on identified neurons of the rat dorsal motor nucleus of the vagus.
Previous evidence suggests that substance P (SP) activates subpopulations of neurons within the dorsal motor nucleus of the vagus (DMV). In this study we aimed at identifying these subpopulations in relation to their gastrointestinal projection organs or vagal branches and characterizing pharmacologically the SP response. Using whole cell patch-clamp recordings from identified gastrointestinal-projecting vagal motoneurons, we found that SP induced an inward current in all neuronal groups except for cecum-projecting cells. The lowest percentage of SP-responding neurons was found in fundus-projecting cells, where SP also had a concentration-response curve that was shifted to the left (P < 0.05). Independently from the projections, the SP response was reduced by sendide and MEN 10,376 and mimicked by a combination of [Sar(9)-Met(O(2))(11)]SP and alpha-neurokinin. SP and alpha-neurokinin also increased the frequency, but not the amplitude, of postsynaptic currents. In conclusion, we demonstrated that SP induces both pre- and postsynaptic effects on DMV neurons via activation of neurokinin NK(1) and NK(2) receptors. The magnitude of the SP response was correlated to the peripheral target organ.
Lewis
M W
MW
Division of Gastroenterology and Department of Physiology, University of Michigan, Ann Arbor, Michigan 48109, USA.
Travagli
R A
RA
D000818:Animals; D000932:Antiemetics / Q000494:pharmacology*; D001933:Brain Stem / Q000166:cytology; D004305:Dose-Response Relationship, Drug; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009046:Motor Neurons / Q000187:drug effects* / Q000502:physiology*; D015288:Neurokinin A / Q000031:analogs & derivatives / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D010446:Peptide Fragments / Q000494:pharmacology*; D011761:Pyrrolidonecarboxylic Acid / Q000031:analogs & derivatives; D051381:Rats; D017207:Rats, Sprague-Dawley; D018040:Receptors, Neurokinin-1 / Q000502:physiology; D018041:Receptors, Neurokinin-2 / Q000502:physiology; D017661:Receptors, Presynaptic / Q000502:physiology; D013373:Substance P / Q000494:pharmacology*; D013779:Tetrodotoxin / Q000494:pharmacology; D014630:Vagus Nerve / Q000166:cytology*
D000932:Antiemetics; D010446:Peptide Fragments; D018040:Receptors, Neurokinin-1; D018041:Receptors, Neurokinin-2; D017661:Receptors, Presynaptic; C069192:neurokinin A(4-10), Tyr(5)-Trp(6,8,9)-Lys(10)-; D013373:Substance P; D013779:Tetrodotoxin; C032292:substance P (6-11); D015288:Neurokinin A; D011761:Pyrrolidonecarboxylic Acid