Biomedical subjects

E Costa

Publications and source records attributed to E Costa.

At least 613 records · Page 34Linked to original sources

PubMed1975

Induction of tyrosine hydroxylase elicited by beta adrenergic receptor agonists in normal and decentralized sympathetic ganglia: role of cyclic 3',5' - adenosine monophosphate.

A subcutaneous injection of an oil suspension of l-epinephrine (270 mumol/kg), dopamine (270 mumol/kg) or l-norepinephrine (270 mumol/kg), when administered with phenoxybenzamine (32 mumol/kg i.p.) to blocl alpha adrenergic effects, increases the cyclic 3', 5'-adenosine monophosphate (cAMP) content in superior cervical ganglia (SCG) of rats. The increase is highest after l-epinephrine and dopamine and is barely detectable after l-norepinephrine; it lasts longer than 2 hours after l-epinephrine, about 30 minutes after dopamine and is fleeting after l-norepinephrine. The duration of the increase in cAMP elicited by l-epinephrine in SCG of rats is dose-related. Furthermore, when the cAMP increase lasts longer than 90 minutes, 48 hours later the tyrosine hydroxylase (TH) activity in SCG is increased. l0Epinephrine (150 mol/kg s.c.) induces TH in decentralized ganglia. One injection of l-isoproterenol (77 mol/kg i.p.) increases cAMP concentrations in intact and decentralized SCG. This increase lasts only 30 minutes and fails to induce TH 48 hours later. However, if the increase of cAMP concentration is prolonged by four successive injections of l-isoproterenol (15 30-minute intervals) the TH activity of intact and decentralized SCG is increased 48 hours later.l-Isoproterenol (four injections of 77 mumol/kg, each) and l-epinephrine (270 mumol/kg) fail to induce TH in the adrenal medulla. dl-Propranolol (125 mumol/kg i.p.) injected 30 minutes before l-isoproterenol blocks the increase of cAMP content and the delayed induction of TH activity in SCG. The elevation of TH activity elicited in SCG by beta adrenergic receptor agonists is always preceded by an increase of cAMP concentration lasting 90 minutes or longer. However, the induction of TH elicited by cold exposure or by reserpine administration can occur without an apparent increase in ganglionic cAMP concentration.

Adrenal Medulla↗

PubMed1975

Effect of thioridazine, clozapine and other antipsychotics on the kinetic state of tyrosine hydroxylase and on the turnover rate of dopamine in striatum and nucleus accumbens.

In rats, a single injection of antipsychotic drugs produced a transitory change in the kinetic state of tyrosine hydroxylase (TH) in striatum and nucleus accumbens. The affinity of TH for 2-amino-4-hydoxy-6,7-dimethyl-5,6,7,8-tetrahydropterine (DMPH4) and the Vmax with respect ot tyrosine were increased. The relative potencies of anti-psychotics to change the kinetics of TH in striatum and nucleus accumbens when injected into rats were measured in the presence of 0.4 mM DMPH4. The doses of methiothepin, pimozide and halopridol which increased the affinity for DMPH4 of striatal TH were lower than those required to produce a similar change in nucleus accumbens. In contrast, thioridazine and clozapine were more effective in nucleus accumbens than in striatum. Chlorpromazine was equally active in these two tissues. Haloperidol increased the turnover rate of dopamine in striatum with doses that are relatively smaller than those required in the nucleus accumbens. Clozapine was more active in increasing turnover rate of dopamine in nucleus accumbens; the activity of chlorpromazine in these two tissues was equal. These results suggest that antipsychotics with high incidence of extrapyramidal side effects affect the nigrostriatal dopaminergic pathway selectively.

Adenylyl Cyclases↗

PubMed1975

Molecular mechanisms in the actions of morphine and viminol (R2) on rat striatum.

Analgesic doses of morphine and viminol R2 increase the turnover rate of dopamine (DA) in rat striatum but fail to increase the striatal concentration of adenosine 3',5'-monophosphate (cAMP) or the affinity of tyrosine hydroxylase (TH) for the pteridine cofactor. When morphine is added to striatal homogenates, it changes neither the basal activity of adenylate cyclase nor the enzyme activation by DA. Similarly to morphine, haloperidol enhances the turnover rate of striatal DA, but unlike morphine it increases the affinity of TH for the pteridine cofactor and blocks the in vitro activation of striatal adenylacte cyclase by DA. Morphine (52 mumol/kg i.p.), viminol R2 (7 mumol/kg i.p.) or haloperidol (2.6 mumol/kg i.p.) fails to increase the striatal cAMP contrations. However (+)-amphetamine (4.8 mumol/kg i.p.) increases DA turnover rate and the striatal cAMP content, but, in doses up to 12.8 mumol/kg i.p., it fails to change the affinity of TH for the pteridine cofactor. This study shows that although (+)-amphetamine, haloperidol and morphine increase the turnover rate of striatal DA each drug possesses a specific profile in its action on molecular mechanisms that control the function of striatal dopaminergic synapses.

Animals↗

PubMed1975