Gabaculine, a specific inhibitor of GABA transaminase, was injected bilaterally into the substantia nigra of rats. One day after injection, GABA was increased 11-fold in the nigra, 6-fold in thalamus and pons-medulla, and 2-fold in pallidum. 5 h after operation, rats showed continuous sniffing and head movement. This behaviour was blocked by a small dose of picrotoxin injected bilaterally into the nigra, but haloperidol (i.p.) was less effective. One day after injection, rats showed high ambulation and this ambulation was blocked by high doses of picrotoxin. On the second day, GABA contents in all regions were less than twice the control level and behaviour had returned to normal. Rats with gabaculine injected into the pallidum or medulla did not show changes of behaviour as seen in rats with injections into the substantia nigra at any of the times. Striatum dopamine turnover was slightly but significantly decreased at 5 h but not at 24 h after intra-nigral injection with gabaculine. The results suggest that gabaculine-induced sniffing and head movement were mediated by nigral GABAergic synapses and were independent of any dopaminergic system, and that the high ambulation at 24 h after operation may have been due to a non-specific effect of abnormal GABA elevation in thalamus and/or nigra.

4-Aminobutyrate Transaminase↗

PubMed1978

Coexistence of bilateral pheochromocytoma and pancreatic islet cell tumor: report of a case and review of the literature.

A 14-year-old Japanese male with a previously undescribed combination of bilateral pheochromocytoma and an islet cell tumor of the pancreas is presented. The combination of endocrine neoplasms in this patient overlaps multiple endocrine neoplasia (MEN) Type 1 and Type 2. A total of 14 reported cases of MEN overlapping Type 1 and Type 2 is reviewed. Of the 14, 7 patients with acromegaly developed a paraganglioma(s), 2 patients with Sipple syndrome had a pituitary adenoma, and in the other 5 patients, an intestinal carcinoid or a pancreatic islet-cell tumor occurred in association with either a thyroid medullary carcinoma or a paraganglioma(s). We believe that the occurrence of MEN overlapping Type 1 and Type 2 is more than a fortuitous association, and can be explained on the basis of the neuroectodermal origin.

Adenoma, Islet Cell↗

PubMed1978

Cataleptic and anticataleptic effects of muscimol and gabaculine injected into globus pallidus and substantia nigra, and interactions with haloperidol or benzodiazepines.

Intranigral injection of muscimol induced hyperactivity in rats and antagonized haloperidol-induced catalepsy. Intranigral injection of gabaculine, an inhibitor of GABA transaminase, induced similar effects 5h after injection, when the nigral GABA content was increased 7-fold. On the other hand, injections of muscimol (30 ng) into the globus pallidus potentiated the cataleptic effect of haloperidol, and muscimol alone in high doses (100 and 200 ng) induced catalepsy. Gabaculine also induced catalepsy of medium intensity and potentiated the effect of haloperidol 24h after injection, when GABA was increased in the globus pallidus as well as in the substantia nigra. Injections of muscimol into either the globus pallidus or substantia nigra increased striatal HVA and enhanced haloperidol-induced elevation of HVA. Three benzodiazepines, nitrazepam, diazepam and chlordiazepoxide administered orally, potentiated the effect of muscimol (30 ng) injected into the globus pallidus and induced catalepsy. A similar effect was not obtained with phenobarbital. It is suggested that stimulation of GABA receptor or increase of GABA content in the sustantia nigra antagonize haloperidol-induced catalepsy by activation of nigral dopaminergic system, and that enhancement of pallidal GABA function induces catalepsy by non-dopaminergic mechanisms. Potentiation of haloperidol-induced catalepsy by benzodiazepines may be due to enhancement of GABA-ergic transmission within the globus pallidus.

4-Aminobutyrate Transaminase↗

PubMed1978