Adrenal involvement in captopril-induced potentiation of morphine analgesia

Abstract: IN 1982, Vidt and colleagues reviewed the pharmacokinetics, mechanisms of action, and therapeutic usefulness of captopril, the first of a new class of antihypertensives, converting-enzyme inhibitor...

Abstract: The use of captopril, an inhibitor of angiotensin-converting enzyme and enkephalinase, was associated with substantial mood elevation in three depressed patients Substances that may alter neuropeptide synthesis or degradation warrant further investigation as therapeutic agents in certain neuropsychiatric disorders

Abstract: Captopril, an angiotensin II converting enzyme (ACE) inhibitor, was evaluated for potential antidepressive activity on the forced swim-induced behavioral despair (immobility) test in mice. Captopril (10.0 and 30.0, mg/kg ip) significantly reduced immobility and mimicked the effects of the antidepressants imipramine (30.0 mg/kg, ip) and mianserin (3.0, 10.0, and 30.0 mg/kg, ip). Captopril increased the motor activity of mice at these same dosages. Naloxone (2.0 mg/kg, ip) blocked the effects of captopril (30.0 mg/kg, ip) in the swim test. These data suggest that captopril has potential antidepressive activity. However, the conclusion is guarded, as the positive effects may be related to motor stimulation. The blockade of the captopril effects by naloxone suggests that brain opioid peptides play a role in this behavioral effect of captopril.

Abstract: The effects of captopril and Ang II on morphine-induced conditioned place preference (CPP) and morphine self-administration in male Wistar rat were investigated. In CPP experiment, injection of captopril before test significantly decreased the difference of the time spent in compartment A between pre- and post-conditioning compared to morphine group. In self- administration experiment number of active lever pressing was significantly greater than passive in morphine group. In captopril group number of active lever pressing was significantly lower than morphine group however, there was not significant difference between active and passive lever pressed number. The results showed that captopril significantly decreased morphine-induced conditional place preference and morphine self-administration but the effect of Ang II was not significant. It can be concluded that RAS may have a role in rewarding properties of morphine.

Abstract: Since 1922 when Wu proposed the use of the Folin phenol reagent for the measurement of proteins, a number of modified analytical procedures utilizing this reagent have been reported for the determination of proteins in serum, in antigen-antibody precipitates, and in insulin. Although the reagent would seem to be recommended by its great sensitivity and the simplicity of procedure possible with its use, it has not found great favor for general biochemical purposes. In the belief that this reagent, nevertheless, has considerable merit for certain application, but that its peculiarities and limitations need to be understood for its fullest exploitation, it has been studied with regard to effects of variations in pH, time of reaction, and concentration of reactants, permissible levels of reagents commonly used in handling proteins, and interfering substances. Procedures are described for measuring protein in solution or after precipitation with acids or other agents, and for the determination of as little as 0.2 gamma of protein.

Abstract: — Angiotensin converting enzyme of rat brain was studied using Hip-His-Leu as substrate. The highest specific activity of the enzyme was associated with the microsomal fraction. The specific activity of the microsomal enzyme in several regions of the rat brain varied significantly. For example, the specific activities of the striatal and pituitary enzymes were about 10-fold greater than that of the cerebral cortical enzyme. The enzyme required chloride ion; moreover, activity was inhibited in the presence of disodium EDTA or O-phenanthroline, effects suggesting that the converting enzyme of brain is a metalloprotein. SQ-20881, a nonapeptide that inhibits converting enzyme in peripheral tissue, was a potent inhibitor of the enzyme of brain. In addition to Hip-His-Leu, the microsomal fraction was capable of liberating C terminal dipeptides from angiotensin I, Hip-Gly-Gly and Z-Gly- Gly-Val. The broad substrate specificity of the enzyme suggests that, in addition to the possible contribution of the enzyme to the brain renin-angiotensin system, other naturally occurring peptides might also be substrates for the enzyme.

Abstract: We have examined enkephalin degradation by solubilized membrane fractions of rat brain. Three distinct enkephalin degrading activities can be partially purified and chromatographically resolved. Aminopeptidase activity gives rise to free tyr, an enzyme designated enkephalinase A generates tyr-gly-gly while a newly reported enzyme activity, enkephalinase B, produces the tyr-gly fragment. Enkephalinase A activity can be completely resolved by DEAE column chromatography from angiotensin converting enzyme activity. This finding, together with a differential sensitivity of angiotensin converting enzyme and enkephalinase A activity to various reagents and salts, demonstrates that they are distinct enzymes.

Abstract: Methionine enkephalin release was evoked by depolarization of slices from rat striatum with potassium. In the presence of 0.1 microM thiorphan [(N(R,S)-3-mercapto-2-benzylpropionyl)glycine], a potent inhibitor of enkephalin dipeptidyl carboxypeptidase (enkephalinase), the recovery of the pentapeptide in the incubation medium was increased by about 100 percent. A similar effect was observed with the dipeptide phenylalanylalanine, a selective although less potent enkephalinase inhibitor. Inhibition of other known enkephalin-hydrolyzing enzymes--aminopeptidase by 0.1 mM puromycin or angiotensin-converting enzyme by 1 microM captopril--did not significantly enhance the recovery of released methionine enkephalin. These data indicate that enkephalinase is critically involved in the inactivation of the endogenous opioid peptide released from striatal neurons.

Abstract: The distribution in rat brain of angiotensin converting enzyme (EC3.4.15.1) using hippuryl-His-Leu as substrate was identical to a dipeptidyl carboxypeptidase present in membranes assayed with Met-enkephalin as substrate. Highest activity occurred in pituitary, followed by cerebellum, corpus striatum, midbrain, pons-medulla, hypothalamus, cerebral cortex and spinal cord. The ratio of products His-Leu/Tyr-Gly-Gly was identical for all regions but differed from His-Leu/Tyr. Angiotensin converting enzyme purified by immunoaffinity chromatography gave a K m for hippuryl-His-Leu of 0.5mM and for Met-enkephalin of 0.1 mM. In the presence of the specific inhibitor of angiotensin converting enzyme, SQ 14,225, the Ki value was 10 −7 M. Present data point to the co-identity of brain angiotensin converting enzyme with the dipeptidyl carboxypeptidase inactivating enkephalin.