Presynaptic alpha 2-adrenoceptors modulate the release of [3H]noradrenaline from rat spinal cord dorsal horn neurones.
Slices of the dorsal half of the rat spinal cord were used to investigate the existence of a noradrenergic feedback modulation of noradrenaline release. After crude preparation of the vertebral column, the spinal cord was ejected by hydraulic pressure and transverse slices were cut. These were preincubated with [3H]noradrenaline during 0.1 Hz electrical stimulation and then superfused and stimulated electrically for two periods. The stimulation-evoked release of [3H]noradrenaline was Ca2+-dependent and tetrodotoxin-sensitive. Pretreatment of the animals with the noradrenergic neurotoxin, DSP-4, reduced the tritium content in the slices and the stimulation-evoked release to less than 10% of the controls. Clonidine (0.01-1 microM) inhibited the evoked overflow by 60% maximally and yohimbine (0.1-1 microM) enhanced it by 160% maximally. The effects of clonidine were antagonized by yohimbine. These results provide evidence that noradrenaline release from spinal cord slices is controlled by an alpha 2-adrenoceptor-mediated, negative feedback mechanism.
Reimann
W
W
Grünenthal GmbH, Abteilung Pharmakologie, Aachen, F.R.G.
Schneider
F
F
D000818:Animals; D001596:Benzylamines / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology; D003000:Clonidine / Q000037:antagonists & inhibitors; D003042:Cocaine / Q000494:pharmacology; D008297:Male; D009474:Neurons / Q000378:metabolism*; D009498:Neurotoxins / Q000494:pharmacology; D009638:Norepinephrine / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000378:metabolism*; D017981:Receptors, Neurotransmitter / Q000378:metabolism*; D013116:Spinal Cord / Q000378:metabolism*; D013779:Tetrodotoxin / Q000494:pharmacology; D014316:Tritium / Q000378:metabolism; D015016:Yohimbine / Q000494:pharmacology; D015031:Zimeldine / Q000494:pharmacology
D001596:Benzylamines; D009498:Neurotoxins; D011942:Receptors, Adrenergic, alpha; D017981:Receptors, Neurotransmitter; D014316:Tritium; D015016:Yohimbine; D015031:Zimeldine; D013779:Tetrodotoxin; D003042:Cocaine; D003000:Clonidine; C012102:DSP 4; D002118:Calcium; D009638:Norepinephrine