Substance P-evoked release of GABA from isolated spinal cord of the newborn rat.
Isolated spinal cords of newborn rats were perfused with artificial cerebrospinal fluid and the effects of substance P and its analogs on the release of endogenous GABA were examined. Application of substance P evoked a dose-dependent release of GABA from spinal cords. The threshold concentration of substance P for induction of a significant increase in the GABA release was 3 microM. The substance P-evoked GABA release was neither blocked by removal of Ca2+ from perfusion medium nor by tetrodotoxin. In contrast, the GABA release evoked by high K+ (90 mM) was abolished in Ca(2+)-free medium, and the GABA release evoked by veratridine (5 microM) was suppressed by tetrodotoxin (1 microM). A GABA uptake inhibitor, cis-4-hydroxynipecotic acid, markedly augmented the GABA release induced by high K+, but not that induced by substance P or veratridine. These results suggest the possibility that a carrier-mediated mechanism might be involved in the GABA release induced by substance P, as well as by veratridine, in the newborn rat spinal cord. Two N-terminal fragments of substance P, substance P free acid and substance P1-10 amide, as well as [D-Arg1,D-Trp7,9,Leu11]substance P (spantide), evoked an increase in the GABA release, whereas substance P1-6, and a C-terminal fragment, substance P5-11 were inactive. Somatostatin and compound 48/80 also evoked a GABA release, which was independent of external Ca2+ and resistant to tetrodotoxin. [D-Pro4,D-Trp7,9,10]substance P4-11 (10-15 microM) inhibited the GABA release evoked by substance P, somatostatin and compound 48/80.(ABSTRACT TRUNCATED AT 250 WORDS)
Sakuma
M
M
Department of Pharmacology, Faculty of Medicine, Tokyo Medical and Dental University, Japan.
Yoshioka
K
K
Suzuki
H
H
Yanagisawa
M
M
Onishi
Y
Y
Kobayashi
N
N
Otsuka
M
M
D000595:Amino Acid Sequence; D000818:Animals; D000831:Animals, Newborn; D001692:Biological Transport / Q000187:drug effects; D002118:Calcium / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D008969:Molecular Sequence Data; D009557:Nipecotic Acids / Q000494:pharmacology; D010446:Peptide Fragments / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012636:Secretory Rate / Q000187:drug effects; D013004:Somatostatin / Q000494:pharmacology; D013116:Spinal Cord / Q000187:drug effects* / Q000378:metabolism; D013268:Stimulation, Chemical; D013373:Substance P / Q000494:pharmacology*; D013779:Tetrodotoxin / Q000494:pharmacology; D014701:Veratridine / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*; D003189:p-Methoxy-N-methylphenethylamine / Q000494:pharmacology
D009557:Nipecotic Acids; D010446:Peptide Fragments; D013373:Substance P; D003189:p-Methoxy-N-methylphenethylamine; D013779:Tetrodotoxin; D013004:Somatostatin; D005680:gamma-Aminobutyric Acid; D014701:Veratridine; C047022:4-hydroxynipecotic acid; D011188:Potassium; D002118:Calcium