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Biomedical subjects

L Z Bito

Publications and source records attributed to L Z Bito.

At least 91 records · Page 5Linked to original sources
PubMed1976

Inhibition of in vitro concentrative prostaglandin accumulation by prostaglandins, prostaglandin analogues and by some inhibitors of organic anion transport.

1. Incubation of rabbit choroid plexus, anterior uvea (iris-ciliary body complex) or slices of kidney cortex in a medium containing tritium-labelled prostaglandin F(2alpha) ([3H]PGF(2alpha) or E1 ([3H]PGE1) results in a four- to thirteenfold concentrative accumulation of 3H activity. 2. Addition of PGF(2alpha, PGF(1) or PGA(1), any one of five PG analogues or a PG precursor, arachidonic acid, at a concentration of 10(-4) M reduced the active accumulation of [3H]PGs by 47-97%. Octanoic acid, at the same concentration, had only a moderate effect on the choroid plexus and no significant inhibitory effect on [3H]PFG(2alpha) accumulation by anterior uvea or kidney cortex. 3. Inhibition was also obtained with 2 mM iodoacetate (under anaerobic conditions) and with 10(-4) M diploretin phosphate, probenecid, iodipamide, indomethacin or dinitrophenol. Perchlorate (10(-4) M) and iodide (10(-4) or 10(-3) M) had no inhibitory effect while 10(-4) M p-aminohippuric acid had a significant inhibitory effect on the kidney cortex at a concentration of 10(-4) M and on the anterior uvea at 10(-3) M. 4. It is concluded that the apparent carrier mediated PG transport systems of the choroid plexus, anterior uvea and kidney cortex are not related to the iodide transport system, but may represent a subcomponent of the iodipamide transport system of these tissues. 5. These results suggest that the systemic distribution and the rate of renal excretion of PGs could be altered by high concentrations of PGs, pharmacologically less active PG analogues, some inhibitors of organic acid transport, and by some inhibitors of PG synthesis and PG action.

Animals↗
PubMed1976

Facilitated transport of prostaglandins across the blood-cerebrospinal fluid and blood-brain barriers.

1. Ventriculo-cisternal perfusions were performed on rabbits with artificial cerebrospinal fluid containing blue dextran and tritium-labelled prostaglandin F(2alpha) ([(3)H]PGF(2alpha)). In order to study the nature of prostaglandin (PG) transfer across the blood-brain barrier, high concentrations of PGF(2alpha) or potential PG transport inhibitors were added to the perfusion fluid after the normal rate of [(3)H]PGF(2alpha) clearance was established.2. The [(3)H]PGF(2alpha) clearance was inhibited by 10(-6) to 10(-3)M PGF(2alpha), PGF(2beta), probenecid, iodipamide or bromcresol green but not by perchlorate.3. The (3)H content of the brain, relative to the (3)H-activity in the ventricular system, was also increased by high concentrations of PGF(2alpha), iodipamide or bromcresol green.4. It is concluded that the removal of PGs from the extracellular fluids of the brain is mediated by saturable, facilitated transport processes across both the choroidal and extrachoroidal regions of the blood-brain barrier system. In the case of the mammalian brain, such facilitated PG transport appears to be the primary mechanism for the termination of the action of these potent, endogenously produced autacoids.

Journal Article↗
PubMed1976

Effects of anti-inflammatory agents and some other drugs on prostaglandin biotransport.

The inhibitory effects of drugs on prostaglandin biotransport were studied by measuring the concentrative accumulation of 3H by rabbit choroid plexuses, segments of anterior uvea and kidney cortex slices after incubation in tissue culture medium containing 3H-prostaglandin F2 alpha. After 10 minutes of incubation in the absence of an inhibitor, the choroid plexus showed a tissue/medium 3H accumulation ratio of 14 +/- 0.7; after 30 minutes of incubation, the anterior uvea and the kidney cortex slices showed accumulation ratios of 6.4 +/- 0.5 and 5.6 +/- 0.1, respectively. The I50 values for inhibition of 3H accumulation by indomethacin were 10, 8 and 12 muM for the three tissues, respectively. Some related drugs-oxyphenbutazone, D-naproxen, l-naproxen, ibuprofen, phenylbutazone and pirprofen-were also found to be effective inhibitors of 3H accumulation (I50 for anterior uvea, 6-28 muM) whereas aspirin, dexamethasone phosphate and penicillin had an inhibitory effect only at much higher concentrations (I50 0.1-2.0 mM). Papaverine, fursemide and probenecid were approximately as effective as the anti-inflammatory organic acids (I50 0.01-0.1 mM), whereas bromcresol green was at least 10-fold more effective. Diphenhydramine and the nonacidic prostaglandin synthesis inhibitors, phenelzine and paracetamol, showed little (I50 greater than 1 mM) or no inhibitory effect. The inhibition of this transport system by some drugs, most notably nonsteroidal anti-inflammatory organic acids, and consequent alterations in the distribution and disposition of prostaglandins must be taken into account in the development of new anti-inflammatory agents and in the interpretation of the mechansim of action and side effects of such drugs.

Animals↗
PubMed1976

The role of transport processes in the distribution and disposition of prostaglandins.

Currently available evidence shows that some cell membranes represent a barrier to passive diffusion of PGs. In contrast, an active transport of PGs was demonstrated across the wall of the rabbit vagina in vitro. Evidence has been obtained indicating that similar carrier-mediated PG transport processes in vivo mediate the uptake of PGs from the circulation into the lung and the removal of these autocoids from the brain and the eye, across the blood--brain and blood--aqueous barriers. It was shown that probenecid, a known inhibitor of PG transport, enhances the effect of PGE1 on the brain, and in general, it appears to alter the distribution and rate of excretion of PGs. The existence of such barriers to the free diffusion of PGs and the saturable, and possibly rate-limiting, transport of these autocoids across some other membranes must be taken into consideration in the design of experiments and in the interpretation of results. Furthermore, the importance of this consideration is emphasized by the observation that many nonsteroidal antiinflammatory agents and PG antagonists are effective inhibitors of PG transport (17,18); hence, they can be expected to affect the distribution and disposition of PGs.

Animals↗
PubMed1975

Impermeability of rabbit erythrocytes to prostaglandins.

Washed rabbit erythrocytes were suspended in Tris-electrolyte buffer containing [3H]prostaglandin (PG) E1, F1alpha, F2alpha, or A1 and one 14C-labeled compound such as sucrose. After up to 24 h of incubation, aliquots of centrifuged, packed cells and supernatant were oxidized and the 3H and 14C samples were counted. The mean sucrose space of the packed cell was 7.4%. After 1 min the E1, F1alpha, and F2alpha spaces were 16, 15.4, and 10.0%, respectively, and showed no increase even after 24 h of incubation at either 23 or 5 degrees C. At 23 degrees C the initial (0.5 min) PGA1 and thiourea spaces were 94 and 75%, respectively, whence the PGA1, but not the thiourea, space declined, reaching 30% at 4 h. The large initial uptake of PGA1 was eliminated at 5 degrees C, while it was accentuated at pH 6.8 or at a PGA1, concentration of 10(-3) M. 14C-Labeled arachidonic, octanoic, and other non-PG fatty acids gave apparent distribution spaces of 140-300%. These results show that PG's can partition into rabbit erythrocyte membranes, but the intracellular volume of the erythrocytes is not freely accessible to these autacoids. The implications of the finding that some cell membranes are impermeable to prostaglandins are discussed.

Animals↗