Substance P-evoked release of acetylcholine from isolated spinal cord of the newborn rat.
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.
Kobayashi
N
N
Department of Pharmacology, Faculty of Medicine, Tokyo Medical and Dental University, Japan.
Sakuma
M
M
Yoshioka
K
K
Onishi
Y
Y
Yanagisawa
M
M
Kawashima
K
K
Otsuka
M
M
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
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