The effects of lesions placed in the lateral hypothalamic area, i.e., interrupting the MFB (as evidenced by a 65% decrease in cortical noradrenaline and serotonin) suggest a pluricompartmentation of brain histamine (HA). The existence of an ascending histaminergic system is indicated by the reductions in l-histidine decarboxylase (H.D.) activity, in [3H]histamine synthesis and in HA content, in the cortex of lesioned rats. Moreover, the decrease in H.D. activity was restricted to the regions rostral to the lesion, without modification caudally. The time-course of the alterations in H.D. activity and in HA content is compatible with a process of anterograde degeneration. In subcellular fractionation studies, the reduction in cortical HA content was found to be mainly confined to the P2 fraction, which contains the synaptosomes. Although the widespread ipsilateral distribution of HA synthesizing terminals resembles that of monoaminergic ones, the absence of reduction in H.D. activity after selective destruction of catecholaminergic and serotoninergic neurons, by 6-hydroxydopamine or 5,6-dihydroxytryptamine respectively, renders likely the existence of specific HA-containing neurons. That the release of the amine from these neurons might be related to the nerve impulse flow is suggested by the transient effects of the lesions which preceded the degenerative process (elevated endogenous HA level and slowed rate of [3H]HA synthesis). In addition, the discrepancy between the reduction in H.D. activity and in HA level after the lesions could be explained by the presence of the amine in another neuronal system and/or in non-neuronal cells, not affected by the lesion. This additional compartment is characterized by a high HA content and a low H.D. activity and could therefore be localized in mast-cells. The respective sizes of these two compartments, estimated by several methods, appear to be approximately the same.

5-Hydroxytryptophan↗

PubMed1976

Neurochemical evidence for histamine acting as a transmitter in mammalian brain.

HA, besides its function in immune processes, is probably a neurotransmitter in mammalian brain. It is synthesized by a specific decarboxylase localized in the cytoplasm of nerve endings. It is stored in synaptic vesicles. Its release might depend on nerve-impulse flow; specific receptors to this amine have been evidenced both electrophysiologically and by the activation of cyclic AMP formation. Lesion studies indicate that histamine-containing neurons might constitute an ascending bundle arising from the brainstem and widely projecting into the whole telencephalon. This disposition, together with neuropharmacological data, suggests that histaminergic neurons, like the monoaminergic ones, might be involved in the control of arousal mechanisms, an idea consistent with the observed fluctuations of the endogenous amine content during the day-night cycle. On the other hand, the investigation of the effect of stress situations on the turnover of HA in brain leads to the conclusion that histaminergic neurons are specifically affected.

Animals↗

PubMed1975

The effect of nerve growth factor on cycle AMP levels in superior cerival ganglia of the rat.

Nerve growth factor (NGF) produces a several-fold increase in the cyclic AMP concentration in rat superior cervical ganglia in organ culture within 5 min. An increase can be seen with as little as 40 ng/ml of NGF. Oxidized NGF is without effect. The increase in the cAMP concentration produced by NGF is prevented by the addition of antiserum to NGF.

Animals↗

PubMed1974