Neurochemistry international
-
We investigated the effect of 5-HT receptor antagonists on mechanical hyperalgesia observed in a neuropathic pain rat model prepared by chronic constriction injury of the sciatic nerve. NAN-190, a 5-HT 1A receptor antagonist, (-)-pindolol, a 5-HT 1A/1B receptor antagonist, and tropisetron, a 5-HT(3/4) receptor antagonist, did not affect the pain threshold in the hyperalgesic hind limb to the same extent as in the normal hind limb. However, sarpogrelate and ketanserin, 5-HT 2A receptor antagonists, significantly elevated the pain threshold in the hyperalgesic hind limb, but not in the normal hind limb. ⋯ Furthermore, the 5-HT 2A receptor specific binding activity of 3H-ketanserin determined for the hyperalgesic hind limb did not differ from that of the normal hind limb. From these results, we propose that the 5-HT 2A receptor in the hyperalgesic hind paw function as an agonist-independent active receptor following constriction of the sciatic nerve, and that sarpogrelate and ketanserin act as inverse agonists of this receptor and suppress its activation. Methysergide may act as a neutral antagonist that blocks the effect of inverse agonists on the 5-HT 2A receptor.
-
According to the astrocyte-neurone-lactate shuttle (ANLS) hypothesis, activated neurones use lactate released by astrocytes as their energy substrate. The hypothesis, based largely on in vitro experiments, postulates that lactate is derived from the uptake by astrocytes of synaptically released glutamate. The time course of changes in lactate, derived from in vivo experiments, is incompatible with the ANLS model. ⋯ This rise in lactate occurs too late to provide energy for neuronal activity. Furthermore, there is no evidence that lactate undergoes local oxidative phosphorylation. In conclusion, under physiological conditions, there is no evidence that lactate is a significant source of energy for activated neurones.