gamma-Aminobutyric acid inhibits the potassium-stimulated release of somatostatin from rat spinal cord slices.
Evidence supports the idea that somatostatin (SO) is a neurotransmitter or neuromodulator of primary afferent neurons involved in nociception. Since gamma-aminobutyric acid (GABA), norepinephrine, and morphine alter nociception at the level of the spinal cord, we examined whether these agents could alter the potassium-stimulated release of somatostatin from rat spinal cord slices. Male Sprague-Dawley rats were decapitated and a 2 cm segment of the lumbar spinal cord removed and chopped into 0.5 x 0.5 mm pieces and perfused at 37 degrees C in individual perfusion chambers with a modified Krebs-bicarbonate buffer at a flow rate of 0.5 ml/min. Perfusates were collected at 2 min intervals and assayed for SO using radioimmunoassay. Exposure of spinal cord tissue to 50 mM KCl resulted in a 3-fold increase in release of SO from a basal level of approximately 0.2 to 0.6 pg/mg tissue/min. This evoked release was calcium dependent. Pre-exposure of tissue to GABA at 10(-4) and 10(-5) M significantly inhibited the potassium-stimulated release of SO, but did not alter basal release. The GABA receptor antagonist, bicuculline methiodide, at 10(-5) but not 10(-6) M attenuated the GABA-induced inhibition of somatostatin release. Bicuculline methiodide alone did not significantly alter either basal or stimulated release. Neither baclofen (10(-5) M, 5 x 10(-5) M), norepinephrine (10(-5) M), nor morphine (10(-5) M) had any significant effect on basal or stimulated release of SO from spinal cord tissue.(ABSTRACT TRUNCATED AT 250 WORDS)
Vasko
M R
MR
Department of Pharmacology and Toxicology, Indiana University School of Medicine, Indianapolis 46202.
Harris
V
V
D000818:Animals; D001418:Baclofen / Q000494:pharmacology; D001640:Bicuculline / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D009020:Morphine / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013004:Somatostatin / Q000378:metabolism*; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism*; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology*
D013004:Somatostatin; D005680:gamma-Aminobutyric Acid; D009020:Morphine; D001418:Baclofen; D011188:Potassium; D009638:Norepinephrine; D001640:Bicuculline