PubMed Health⌕ Search

Biomedical subjects

J M Fujimoto

Publications and source records attributed to J M Fujimoto.

At least 127 records · Page 7Linked to original sources
PubMedDate not supplied

Acute cross-tolerance to opioids in heroin delta-opioid-responding Swiss Webster mice.

It is generally thought that the mu receptor actions of metabolites, 6-monoacetylmorphine (6MAM) and morphine, account for the pharmacological actions of heroin. However, upon intracerebroventricular (i.c.v.) administration in Swiss Webster mice, heroin and 6MAM act on delta receptors while morphine acts on mu receptors. Swiss Webster mice made tolerant to subcutaneous (s.c.) morphine by morphine pellet were not cross-tolerant to s.c. heroin (at 20 min in the tail flick test). Now, opioids were given in combination, s.c. (6.5 h) and i.c.v. (3 h) preceding testing the challenging agonist i.c.v. (at 10 min in the tail flick test). The combination (s.c. + i.c.v.) morphine pretreatment induced tolerance to the mu action of morphine but no cross-tolerance to the delta action of heroin, 6MAM and DPDPE and explained why morphine pelleting did not produce cross-tolerance to s.c. heroin above. Heroin plus heroin produced tolerance to delta agonists but not to mu agonists. Surprisingly, all combinations of morphine with the delta agonists produced tolerance to morphine which now acted through delta receptors (inhibited by i.c.v. naltrindole), an unusual change in receptor selectivity for morphine.

Analgesics, Opioid↗
PubMedDate not supplied

Lack of inhibitory effect of aprotinin and bacitracin on the spinal release of Met-enkephalin induced by intraventricular beta-endorphin.

We have previously reported that administration of beta-endorphin intraventricularly in the rat increases the release of immunoreactive Met-enkephalin from the spinal cord. To further eliminate the possibility that the increase in Met-enkephalin might arise from the degradation of beta-endorphin injected, the effect of peptidase inhibitors, aprotinin and bacitracin, on the spinal fluid content of Met-enkephalin released by intraventricular beta-endorphin was studied using an intrathecal perfusion technique in urethane anesthetized rats. Inhibition of peptidases by intraventricular aprotinin and bacitracin did not decrease nor enhance the increased content of Met-enkephalin in the spinal perfusate produced by intraventricular beta-endorphin. The result indicates that the Met-enkephalin arises from neuronal release in the spinal cord rather than from degradation of the beta-endorphin injected intraventricularly.

Animals↗
PubMedDate not supplied

Tolerance to cadmium in the abdominal stretch response: a comparative study of cadmium and acetic acid.

The intraperitoneal injection of cadmium (Cd) in mice produces a characteristic abdominal stretch response similar to that observed with acetic acid. Morphine, clonidine, and tripelennamine ED50 values were the same for inhibition of the response to Cd and to acetic acid. The ED50 values for aspirin and indomethacin were lower against the Cd than the acetic acid response. On repeated injections, Cd did but acetic acid did not produce tolerance to itself. Furthermore, the mice made tolerant to Cd were not cross-tolerant to acetic acid, but the acetic-acid-treated mice were cross-tolerant to Cd. These results suggest that Cd and acetic acid may produce the stretch response through different mechanisms, and the Cd-induced response might serve as a screening test for aspirin-like agents.

Abdominal Muscles↗
PubMedDate not supplied

Enhanced naloxone distribution to the brain by morphine pretreatment in mice.

An increase in the disposition of naloxone to the mouse brain was observed for animals previously exposed to morphine. Compared to controls, mice receiving morphine sulfate (10 mg/kg, sc) 3 hr prior to naloxone had a 28% increase in naloxone concentration in brain (200 to 260 pmol of naloxone per g of brain) 10 min after 3H-naloxone-HCl (0.4 mg/kg, 11.0 micronCi/kg, sc) administration. Also, if similar morphine-pretreated mice received a second dose of morphine sulfate (1.0 mg/kg, sc) concurrent with 3H-naloxone-HCl, the morphine-induced enhancement of 3H-naloxone concentration in brain was unaltered. This drug-treatment protocol paralleled that used by others in pA2-analgesia assays to demonstrate sensitization to naloxone for morphine-pretreated animals. In prior (3 hr) morphine-treated animals, administration of 3H-naloxone-HCl (0.1 mg/kg, 33.3 micronCi/kg) iv resulted in an 11.0% increase in 3H-naloxone brain concentration after 1 min. Thus, the enhancement of naloxone brain concentration was independent of the route of naloxone administration. No enhancement of 3H-naloxone brain concentration could be seen 24 hr after morphine sulfate pretreatment (10 mg/kg, sc), a decline in the effect similar to that seen for morphine-induced sensitization to naloxone. Finally, when morphine pellet-implanted mice (75 mg of morphine base, 72 hr) were administered 3H-naloxone-HCl (0.4 mg/kg, 10.0 micronCi/kg, sc), only a 22.5% enhancement of 3H-naloxone concentration in brain was obtained, as opposed to a reported 8-fold increase in the potency of naloxone. Thus, although a number of similarities exist between the enhancement by morphine of naloxone concentration in brain and its sensitization to the antagonistic activity of naloxone, a quantitative correlation appears to be lacking between the two phenomena.

Animals↗
PubMedDate not supplied

Preliminary characterization of enzymes for reduction of naloxone and naltrexone in rabbit and chicken liver.

The enzyme systems involved in the reduction of the narcotic antagonists, naloxone and naltrexone, were studied from the liver of chicken and rabbit. These secies were chosen because the relative amounts of diastereoisomeric products formed by enzymatic reduction between these species are so different; naloxone and naltrexone are converted in the chicken to 6alpha-naloxol and 6alpha-naltrexol, respectively, and in the rabbit to 6beta-naloxol and 6beta-naltrexol, respectively. In the present study, the enzymes for carrying out this reduction were found to require NADPH and to occur in the soluble fraction of liver homogenates. These enzymes were precipitated at 60-70% ammonium sulfate saturation for the chicken and at 50-60% for the rabbit. Differential sensitivity to inhibitors could be shown. For example, the rabbit enzyme was more sensitive to inhibition by morphine than was the chicken enzyme. The reverse order of sensitivity was seen with ketamine. These differences in properties between the chicken and rabbit liver enzymes indicate that the alpha- and beta-hydroxy product stereoselectivity arises from two different enzymes carrying out the reduction.

Animals↗
PubMedDate not supplied

The stimulatory effect of morphine on reduction of naltrexone to 6 alpha-naltrexol in the guinea pig.

The enzymatic reduction of naltrexone proceeds more rapidly for formation of 6 alpha- than 6 beta-naltrexol in vitro in the guinea pig hepatic cytosol preparation. This paper describes the effect shown by addition of morphine to this formation; stimulation of the stereo-selective formation of 6 alpha-naltrexol. The enzyme activity for formation of 6 alpha-naltrexol was greatest in the 50--70% ammonium sulfate-precipitated fraction, whereas that for 6 beta-naltrexol formation peaked in the 40--60% fraction. When the 60--70% ammonium sulfate fraction was incubated with naltrexone, it was found that the Vmax was greatest for formation of 6 alpha-naltrexol when NADPH was added as the cofactor, less with the glucose-6-phosphate dehydrogenase NADPH-generating system, and least with NADH. When 10 mM morphine was added, the stimulation of 6 alpha-naltrexol formation occurred when either NADPH or NADH was added as cofactor. Inasmuch as enzyme activity with NADH in the absence of morphine was low, the relative stimulation by morphine was greater for the NADH than for the NADPH system. Also, when both NADPH and NADH were added in the same assay mixture, the predominant effect appeared to be manifested by the NADH system. Experiments in vivo indicated that coadministration of morphine intravenously with 3H-naltrexone did not produce stimulation of 6 alpha-naltrexol formation as measured in either bile or urine. On the other hand, the previous results on stimulation of 6 alpha-naloxol formation from naloxone were confirmed in vivo.

Animals↗