title: Substance P-evoked release of acetylcholine from isolated spinal cord of the newborn rat.
abstract: Isolated spinal cords of newborn rats were perfused with artificial cerebrospinal fluid and the release of endogenous acetylcholine was measured using high-performance liquid chromatography with an electrochemical detection system. Application of high-K+ (90 mM) medium evoked about an eight-fold increase in the acetylcholine release, and the K(+)-evoked release was Ca2+ dependent. Veratridine (20 microM) also evoked about a four-fold increase in the acetylcholine release, and this increase was suppressed by 0.2 microM tetrodotoxin. Application of substance P at 0.3-3 microM evoked a concentration-dependent release of acetylcholine. The substance P-evoked acetylcholine release was Ca2+ dependent and abolished by tetrodotoxin. Neurokinin A, neurokinin B, acetyl-Arg6-septide and senktide (3 microM each) also evoked a release of acetylcholine. Electrophysiological experiments using isolated spinal cords of newborn rats showed that bath application of substance P induced a depolarization of motoneurons, which was enhanced by edrophonium. This enhancement of substance P-induced depolarization by edrophonium disappeared in a low-Ca2+ medium or in the presence of atropine and dihydro-beta-erythroidine. In the presence of edrophonium and dihydro-beta-erythroidine, substance P induced an inhibition of monosynaptic reflex, and this inhibition was abolished by atropine. These results suggest that substance P and other tachykinins induce a release of acetylcholine from the newborn rat spinal cord by exciting cholinergic neurons.
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Tokyo Medical and Dental University, Japan.
authors.forename: N
authors.initials: N
authors.lastname: Kobayashi
authors.forename: M
authors.initials: M
authors.lastname: Sakuma
authors.forename: K
authors.initials: K
authors.lastname: Yoshioka
authors.forename: Y
authors.initials: Y
authors.lastname: Onishi
authors.forename: M
authors.initials: M
authors.lastname: Yanagisawa
authors.forename: K
authors.initials: K
authors.lastname: Kawashima
authors.forename: M
authors.initials: M
authors.lastname: Otsuka
mesh_terms: D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D000831:Animals, Newborn; D002118:Calcium / Q000502:physiology; D004079:Dihydro-beta-Erythroidine / Q000494:pharmacology; D004491:Edrophonium / Q000494:pharmacology; D015288:Neurokinin A / Q000494:pharmacology; D015287:Neurokinin B / Q000494:pharmacology; D010446:Peptide Fragments / Q000494:pharmacology; D010830:Physostigmine / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012636:Secretory Rate / Q000187:drug effects; D013116:Spinal Cord / Q000187:drug effects* / Q000378:metabolism; D013268:Stimulation, Chemical; D013373:Substance P / Q000031:analogs & derivatives / Q000494:pharmacology*; D013779:Tetrodotoxin / Q000494:pharmacology; D014701:Veratridine / Q000494:pharmacology
chemical_list: D010446:Peptide Fragments; C054724:senktide; C066071:septide, acetyl-Arg(6)-; D004079:Dihydro-beta-Erythroidine; D013373:Substance P; D013779:Tetrodotoxin; D004491:Edrophonium; D014701:Veratridine; D015288:Neurokinin A; D015287:Neurokinin B; D010830:Physostigmine; D000109:Acetylcholine; D011188:Potassium; D002118:Calcium