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Biomedical subjects

A Guidotti

Publications and source records attributed to A Guidotti.

At least 289 records · Page 16Linked to original sources
PubMed1976

Cyclic AMP content and regulation of tyrosine-3-mono-oxygenase in rat striatum.

The unilateral transection of nigro striatal dopaminergic axons produced a short lasting (15-30 min) increase in the affinity of striatal tyrosine 3-mono-oxygenase (TH), for a synthetic pteridine cofactor (DMPH4). The kinetic changes of striatal TH were paralleled by an increase of striatal cAMP content. Apomorphine (10 mg/kg i.p.) failed to block the activation of TH by cerebral hemisection. Haloperidol (5 mg/kg i.p.) and reserpine (5 mg/kg i.p.) also elicited a sudden and similar change in striatal TH activity but this response occurred without an increase in the cAMP content and lasted for longer than 2 hrs. If the hemisection of nigrostriatal pathway was performed after haloperidol or reserpine injection the activation of TH produced by these two drugs was reversed rapidly (about 30 minutes). Pretreatment with haloperidol or reserpine prevented the increase of striatal cAMP following cerebral hemisection. Moreover, haloperidol injected 30 min after cerebral hemisection failed to change the TH kinetic properties in the striatum ipsilateral to the lesion but it changed striatal TH in the side contralateral to the lesion. These results suggest that the increase in the affinity of striatal TH for the pteridine cofactor elicited by cerebral hemisection is not related to a lack of stimulation of DA autoreceptors. Moreover these experiments provide an evidence that postsynaptic dopamine receptors play a role in the activation of striatal TH elicited by haloperidol.

Animals↗
PubMed1975

Dopamine-sensitive adenylyl cyclase in human caudate nucleus. A study in control subjects and schizophrenic patients.

Striatal adenylyl cyclase activity from autopsied human brain is selectively stimulated by low concentrations of dopamine. Under the experimental conditions used, norepinephrine was about three times less potent than dopamine. Histamine and serotonin were ineffective. The stimulation by dopamine was competitively inhibited by haloperidol. There was no difference between the basal adenylyl cyclase activity or its level after dopamine stimulation between nine control subjects without a psychiatric history and seven patients with chronic schizophrenia.

Adenosine Triphosphate↗
PubMed1975

The regulation of striatal tyrosine hydroxylase. Effects of gamma hydroxybutric acid and healperidol.

Gamma-hydroxybutyric acid (GHBA) in doses that increased the striatal dopamine (DA) content of rat brain failed to increase the affinity of striatal tyrosine hydroxylase (TH) for its pterdine cofactor or to change the sensitivity of the enzyme to the inhibition by DA. Haloperidol (1 mg/kg) decreased the apparent Km of striatal TH for the pteridine cofactor. However, when GHBA was injected before haloperidol it prevented the decrease in the apparent Kn of TH, in a dose related manner. In vitro GHBA (10(-4) M) neither changed the stimulation of the striatal adenylyl cyclase by DA nor its inhibition by haloperidol. These results suggest that in striatal dopaminergic terminals the Kn of TH for the pteridine cofactor is regulated by an molecuular mechanism which requires that the impulse flow in the DA neurons is unimpaired.

Adenylyl Cyclases↗
PubMed1975

Evidence for an involvement of GABA in the mediation of the cerebellar cGMP decrease and the anticonvulsant action diazepam.

Subcutaneous injections of isoniazid or picrotoxin increase the cerebellar content of 3',5'-cyclic guanosine monophosphate (cGMP) without changing the 3',5'-cyclic adenosine monophosphate cAMP. This increase was dose dependent and the threshold for the cGMP increase was lower than that for convulsions. In cerebellum the increase of cGMP content elicited by isoniazid but not that caused by picrotoxin was paralleled by a decrease of GABA content. Diazepam doses starting from 1.74 mumol/kg intraperitoneally produced a dose dependent decrease of cerebellar cGMP concentration without changing cAMP or GABA content. Smaller doses of diazepam (0.5 mumol/kg i.p.)failed to decrease the basal cerebellar content of cGMP. However, this dose of diazepam antagonized the increase of cGMP produced by isoniazid but not that produced by picrotoxin. Higher doses of diazepam were necessary to block the increase of cerebellar cGMP elicited by picrotoxin. Low doses of diazepam (0.14 mumol/kg) antagonized the convulsions in 50% of the rats injected with 3.3 mmol/kg of isoniazid. The doses of diazepam required to block picrotoxin, pentylenetetrazol or strychnine convulsions were 7, 25 and 40 times higher than those required to block isoniazid convulsions, respectively. Desmethyldiazepam, chloridiazepoxide, oxazepam were also several times more potent in antagonizing isoniazid than picrotoxin, pentylenetetrazol, or strychnine convulsions. In contrast, barbiturates were equipotent against all the convulsants studied. These experiments suggest that diazepam may act in the CNS either by altering the disposition of endogenous GABA or by mimicking the action of GABA at specific synaptic receptors.

Aminobutyrates↗
PubMed1975

Further evidence for a cAMP dependent regulation of tyrosine-3-monoxygenase induction in adrenal medulla: effect of denervation.

Unilateral adrenal denervation caused a gradual decrease of adenylate cyclase activity in rat adrenal medulla. The extent of the increase in adrenal medullary 3',5'-cyclic adenosine monophosphate (cAMP) content elicited by injections of carbamylcholine declined gradually folling adrenal denervation. Three or nine days after denervation carbamylcholine caused rise of cAMP and a delayed increase of tyrosine-3-mono-oxygenase (TH) activity of similar magnitude in intact and denervated adrenal medullae. However, after an interval of 15 days or longer following denervation the increase in TH activity elicited by carbamylcholine was greatly reduced. These results support previous proposals that cAMP is involved as a second messenger in the trans-synaptic induction of TH.

Adenylyl Cyclases↗
PubMed1975

Protein kinase activation as an early event in the trans-synaptic induction of tyrosine 3-monooxygenase in adrenal medulla.

An increase of cAMP/cGMP concentration ratio is the earliest stimulus-coupled biochemical change that has been measured in the adrenal medulla during the trans-synaptic induction of tyrosine 3-monooxygenase [EC 1.14.16.2; L-tyrosine, tetrahydropteridine:oxygen oxidoreductase (3-hydroxylating)]. In adrenal medulla of rats receiving reserpine alone (16 mumol/kg intraperitoneally) or reserpine and propranolol (40 mumol/kg intraperitoneally 30 min before reserpine), or exposed to 4 degrees for 4 hr, the extent and duration of the increase of the cAMP/cGMP concentration ratio exceeds the critical value that is required to activate the protein kinases (EC 2.7.1.37; ATP:protein phosphotransferase). Gel filtration experiments indicate that during this activation, the catalytic subunit of the protein kinase (low-molecular-weight enzyme) is released from the holoenzyme. The activation of protein kinase lasts longer than the increase in the cAMP/cGMP concentration ratio and appears to be an obligatory early event that mediates the increase of tyrosine monooxygenase synthesis. The trans-synaptic induction of the monooxygenase in adrenal medulla appears to be due to an increased synthesis of the enzyme;the rate for monooxygenase degradation is proportional to the number of enzyme molecules that are present at various stages of the induction process.

Adrenal Medulla↗