Adenosine analogs do not inhibit the potassium-stimulated release of substance P from rat spinal cord slices.
Adenosine agonists produce antinociception when injected directly onto the spinal cord of rats and mice. One mechanism to account for this effect could be inhibition of neurotransmitter release from nociceptive sensory neurons. Consequently, we studied whether these agents could inhibit the potassium stimulated release of one such transmitter, substance P, from rat spinal cord slices. A 2 cm section of lumbar spinal cord was dissected from male Sprague-Dawley rats, chopped into 0.5 x 0.5 mm sections and perfused at 37 degrees C with a modified Krebs bicarbonate buffer containing either 3.5 mM, 30 mM, or 50 mM KCl in the presence and absence of various adenosine analogs. Perfusates, collected every 2 min, were assayed for substance P by radioimmunoassay. Exposure of tissue to 50 mM KCl produced an approximate three-fold increase in the release of substance P over basal release. This increase in release was calcium dependent. Perfusion of spinal cord tissues with either adenosine (10(-3) M). N6-cyclohexyladenosine (10(-5) M or 5 x 10(-5) M), 5'-N-ethylcarboxamide adenosine (10(-5) M) or L-N6-phenylisopropyladenosine (10(-5) M) did not significantly alter basal or potassium-stimulated release of SP when compared to controls. In contrast to the adenosine agonists, exposure of the spinal cord tissue to 10(-5) M morphine significantly reduced the potassium-stimulated release of substance P. Pretreatment of the slices with 10(-5) M theophylline or 8-phenyl-theophylline did not significantly attenuate the inhibition of substance P release produced by morphine. Theophylline alone (10(-5) M) had no significant effect on either basal or potassium-stimulated release of SP.(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Pharmacology and Toxicology, Indiana University School of Medicine, Indianapolis 46202.
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D000241:Adenosine / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D000818:Animals; D066298:In Vitro Techniques; D008297:Male; D009020:Morphine / Q000494:pharmacology; D009475:Neurons, Afferent / Q000187:drug effects / Q000378:metabolism; D018377:Neurotransmitter Agents / Q000378:metabolism; D011188:Potassium / Q000494:pharmacology*; D011189:Potassium Chloride / Q000494:pharmacology; D011863:Radioimmunoassay; D051381:Rats; D011919:Rats, Inbred Strains; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism*; D013373:Substance P / Q000378:metabolism*; D013806:Theophylline / Q000494:pharmacology
D018377:Neurotransmitter Agents; D013373:Substance P; D011189:Potassium Chloride; D009020:Morphine; D013806:Theophylline; D000241:Adenosine; D011188:Potassium