Release of substance P from the cat spinal cord.
1. The present experiments examine the physiology and pharmacology of the release of substance P-like immunoreactivity (SP-l.i.), from the spinal cord in the halothane-anaesthetized, artificially ventilated cat. 2. Resting release of SP-l.i. was 36 +/- 4 fmol/30 min (mean +/- S.E.; n = 106). Bilateral stimulation of the sciatic nerves at intensities which evoked activity in fibres conducting at A beta conduction velocities (greater than 40 m/s), resulted in no change in blood pressure, pupil diameter or release of SP-l.i. Stimulation intensities which activate fibres conducting at velocities less than 2 m/s resulted in increased blood pressure, miosis and elevated release of SP-l.i. (278 +/- 16% of control). 3. The relationship between nerve-stimulation frequency and release was monotonic up to approximately 20 Hz. Higher stimulation frequencies did not increase the amounts of SP-l.i. released. At 200 Hz there was a reduction. 4. Capsaicin (0.1 mM) increased the release of SP-l.i. from the spinal cord and resulted in an acute desensitization to subsequent nerve stimulation. This acute effect was not accompanied by a reduction in spinal levels of SP-l.i. measured 2 h after stimulation. 5. Cold block of the cervical spinal cord resulted in an increase in the amounts of SP-l.i. released by nerve stimulation. 6. Pre-treatment with intrathecal 5,6-dihydroxytryptamine (300 micrograms) 7 days prior to the experiment caused a reduction in the dorsal and ventral horn stores of SP-l.i., but had no effect on the release of SP-l.i. evoked by nerve stimulation. Similar pre-treatment with intrathecal capsaicin (300 micrograms) resulted in depletion of SP-l.i. in the dorsal but not in the ventral horn of the spinal cord and diminished the release of SP-l.i. evoked by nerve stimulation. 7. Intense thermal stimulation of the flank resulted in small (20-35%), but reliable increases in the release of SP-l.i. above control. 8. Putative agonists for the opioid mu-receptor (morphine, 10-100 microM; sufentanil, 1 microM), and for the delta-receptor (D-Ala2-D-Leu5-enkephalin, 1-10 microM; D-Pen2-D-Pen5-enkephalin, 10 microM), but not the kappa-receptor (U50488H, 100-1000 microM), produced a dose-dependent, naloxone-reversible reduction of the evoked, but not of the resting release of SP-l.i. (-)-Naloxone, but not (+)-naloxone, resulted in a significant increase in evoked but not resting SP-l.i. release.(ABSTRACT TRUNCATED AT 400 WORDS)
D015115:5,6-Dihydroxytryptamine / Q000494:pharmacology; D000700:Analgesics / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure; D002211:Capsaicin / Q000494:pharmacology; D002415:Cats; D005260:Female; D036341:Intercellular Signaling Peptides and Proteins; D008297:Male; D009270:Naloxone / Q000494:pharmacology; D018377:Neurotransmitter Agents / Q000494:pharmacology; D010455:Peptides / Q000378:metabolism; D012584:Sciatic Nerve / Q000502:physiology; D013116:Spinal Cord / Q000502:physiology*; D013373:Substance P / Q000378:metabolism*; D013566:Sympathomimetics / Q000494:pharmacology; D013696:Temperature; D013997:Time Factors
D000700:Analgesics; D036341:Intercellular Signaling Peptides and Proteins; D018377:Neurotransmitter Agents; D010455:Peptides; D013566:Sympathomimetics; C016116:substance P-like peptides; D013373:Substance P; D009270:Naloxone; D002211:Capsaicin; D015115:5,6-Dihydroxytryptamine