Release of substance P from the cat spinal cord.

Abstract

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)