Presynaptic regulation of neurotransmitter release in the brain: facts and hypothesis

Mismatches between neurotransmitter and receptor localizations in brain: observations and implications.

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)

https://physoc.onlinelibrary.wiley.com/doi/pdf/10.1113/jphysiol.1987.sp016731

Release of substance P from the cat spinal cord.

An immunohistochemical study of neuronal populations containing neuropeptides or γ-aminobutyrate within the superficial layers of the rat dorsal horn

Recently, antisera that recognize unique epitopes of the cloned mu-, delta-, and kappa-opioid, receptors (MOR, DOR, KOR, respectively) have been developed. In the present study MOR-, DOR-, and KOR-like immunoreactivities (LIs) were examined in rat dorsal root ganglia (DRGs, L4-5) after injection of carrageenan (CAR) into the hindpaw. In normal control rats 20.9%, 13.5%, and 9% of the DRG neurons contained MOR-, DOR-, KOR-LI, respectively. A marked upregulation in MOR-LI was observed in DRG neurons 1 and 3 d after inflammation. In contrast, CAR induced a distinct downregulation in DOR- and KOR-LIs. MOR-, DOR-, and KOR-LIs were preferentially localized in small DRG neurons. MOR-LI was often located in patches in the cytoplasm, and in some cells close to the somatic plasmalemma. However, DOR- and KOR-LIs mainly showed a diffuse staining pattern within cytoplasm. Two or even all three receptors could sometimes be found to coexist in DRG neurons. In the spinal cord, these receptors were mainly confined to the superficial dorsal horn, with a somewhat diffuse staining which was strong for MOR-LI, and weak for KOR-LI. DOR-LI had distinctly punctate, varicose distribution. CAG induced-alterations in opioid receptor staining in spinal cord were much less pronounced than those in the DRGs with a small increase in MOR-LI and a slight decrease in DOR-LI ipsilaterally. There was an accumulation of all three types of receptors in the sciatic nerve both proximal and distal to the ligation site as early as 2 hr, indicating both antero- and retrograde transport of multiple opioid receptors. However, DOR-LI accumulation was stronger than that of MOR- and KOR-LIs. Taken together, these results suggest that all three opioid receptors are involved in the response to inflammation and that they may play different roles in this pathological state. The coexistence of MOR, DOR, and KOR in at least some primary sensory neurons provides a substrate for functional interactions between these receptors.

https://www.jneurosci.org/content/jneuro/15/12/8156.full.pdf

Expression of mu-, delta-, and kappa-opioid receptor-like immunoreactivities in rat dorsal root ganglia after carrageenan-induced inflammation

Effect of dorsal rhizotomy on the autoradiographic distribution of opiate and neurotensin receptors and neurotensin-like immunoreactivity within the rat spinal cord.

J.S. Kelly

Papers

Effect of dorsal rhizotomy on the autoradiographic distribution of opiate and neurotensin receptors and neurotensin-like immunoreactivity within the rat spinal cord.