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A S Basile

Publications and source records attributed to A S Basile.

At least 19 recordsLinked to original sources
PubMed1992

Differential effects of cytochrome P-450 induction on ligand binding to sigma receptors.

The identity of the sigma receptor as a form of cytochrome P-450 was investigated in rats treated with 3-methylcholanthrene or phenobarbital. The density of [3H]N,N'-di(o-tolyl)guanidine (DTG) binding to sigma 2 receptors in hepatic subcellular fractions increased following both treatments, while [3H](+)-pentazocine binding to sigma 1 receptors was unchanged. Furthermore, proadifen and piperonyl butoxide inhibited [3H](+)-pentazocine and [3H]DTG binding with low potency. The low affinity of cytochrome P-450 inhibitors for sigma receptors, the similar degree of enhancement of [3H]DTG binding by agents with disparate cytochrome P-450 induction profiles and the lack of change in [3H](+)-pentazocine binding are inconsistent with the identity of the sigma receptor as a cytochrome P-450.

Animals↗
PubMed1992

Modulation of (+)-[3H]pentazocine binding to guinea pig cerebellum by divalent cations.

The ability of cations to modulate the binding of the sigma 1 receptor-selective ligand (+)-[3H]pentazocine to guinea pig cerebellum was investigated. Di- and trivalent cations biphasically inhibited (+)-[3H]pentazocine binding, revealing multiple affinity states. The rank order of potency of these cations (based on the high affinity component of inhibition) was Zn2+ > Co2+ >> La3+ = Ni2+ = Cd2+ = Mn2+ = Gd2+ > Ba2+ = Sr2+ >> Mg2+ > Ca2+. The inhibition of 1,3-[3H]di(2-tolyl)guanidine binding to the sigma 2 receptor by these cations differed qualitatively and quantitatively from their effects on (+)-[3H]pentazocine binding. Although monovalent cations decreased the Kd for (+)-[3H]pentazocine binding, divalent cations split (+)-[3H]pentazocine binding into low and high affinity components. The Bmax of the high affinity component decreased with increasing divalent cation concentrations. Both mono- and divalent cations significantly reduced the rate of association of (+)-[3H]pentazocine with the sigma 1 receptor without altering the dissociation rate. (+)-[3H]Pentazocine binding was not altered by guanine nucleotides or by treatment with cholera or pertussis toxins. However, nonselective cation channel blockers (cinnarizine, hydroxyzine, prenylamine, amiodarone, and proadifen) potently inhibited (+)-[3H]pentazocine binding. These results indicate that physiologically relevant concentrations of divalent cations allosterically modulate (+)-[3H]pentazocine binding to the sigma 1 receptor, to reveal multiple affinity states. These sites do not represent sigma 1 to sigma 2 subtype interconversion or ternary complex formation with guanine nucleotide-binding proteins. However, the rank order of cation potency and the inhibition of binding by cation channel blockers is consistent with a potential role for sigma receptors as constituents of cation channels.

Animals↗
PubMed1991

Elevated brain concentrations of 1,4-benzodiazepines in fulminant hepatic failure.

BACKGROUND: Increased gamma-aminobutyric acid (GABA) neurotransmission has been implicated in the pathogenesis of hepatic encephalopathy. The mechanism by which GABA-ergic activity is increased in hepatic failure is unclear, but recent studies in animals with encephalopathy due to fulminant hepatic failure suggest that GABA-ergic neurotransmission may be increased by the presence of elevated concentrations of benzodiazepine agonists such as diazepam and N-desmethyldiazepam. METHODS AND RESULTS: Samples of frontal cortex were obtained at autopsy from 11 patients with hepatic encephalopathy who died of acetaminophen-induced fulminant hepatic failure and 8 patients who died of cardiovascular disease or trauma. None of the 19 patients had received benzodiazepines while hospitalized. Chromatographic analyses of extracts of these samples revealed 4 to 19 peaks representing substances that inhibited the binding of a radiolabeled imidazobenzodiazepine ([3H]flumazenil) to its receptors. Several of these peaks had retention times corresponding to those of known 1,4-benzodiazepines. Ultraviolet- and mass-spectroscopic analysis confirmed that two of these peaks represented diazepam and N-desmethyldiazepam. The patients who died of fulminant hepatic failure could be divided into two groups: six who had had significantly elevated brain concentrations (2-fold to 10-fold higher than normal) of substances inhibiting the binding of [3H]flumazenil and five who had normal concentrations. CONCLUSIONS: Brain concentrations of substances inhibiting the binding of [3H]flumazenil to its receptors are increased in some patients with hepatic encephalopathy due to fulminant hepatic failure. The origin of these substances is unknown, but these findings provide a rational basis for trials of benzodiazepine-receptor antagonists in the management of this disorder.

Adult↗
PubMed1991

Inhibition of substrate oxidation in mitochondria by the peripheral-type benzodiazepine receptor ligand AHN 086.

The effects, of the benzodiazepines RO5-4864, AHN 086, PK 11195 and clonazepam on respiration of mitochondria from heart, kidney, and liver were studied. ADP-stimulated respiration of heart mitochondria was the most sensitive to inhibition by AHN 086; clonazepam was not inhibitory. Several respiratory chain segment activities of submitochondrial particles were insensitive to AHN 086, except for NADH oxidase which was partially inhibited. However, in contrast to submitochondrial particles, the succinate-cytochrome c oxidoreductase activity in intact mitochondria was inhibited by AHN 086, suggesting an effect at the substrate transport level. Phosphate-induced, succinate-dependent swelling was also inhibited by AHN 086 it was not affected by clonazepam. Uncoupled ATP hydrolysis was partially inhibited by RO5-4864, AHN 086, and clonazepam. It is suggested that there is an unspecific inhibition of NADH oxidase and ATP hydrolysis by these benzodiazepines and a specific inhibition on oxidizable substrate transport by the peripheral-type benzodiazepine AHN 086.

Adenosine Triphosphate↗
PubMed1991

The contribution of endogenous benzodiazepine receptor ligands to the pathogenesis of hepatic encephalopathy.

The involvement of the gamma-aminobutyric acid A(GABAA) receptor complex in the pathogenesis of hepatic encephalopathy (HE) was examined in galactosamine-treated rabbits with HE caused by fulminant hepatic failure. Radioligand binding to the constituent components of the GABAA receptor complex was unchanged in rabbits with HE. However, partially purified extracts from encephalopathic rabbit brain were approximately three times more potent in inhibiting [3H]Ro 15-1788 binding to benzodiazepine (BZ) receptors than extracts from control rabbits. The inhibition of radioligand binding to the BZ receptor produced by these extracts was competitive and reversible and was significantly enhanced by GABA. Further purification of these extracts by high-performance liquid chromatography (HPLC) indicated that the inhibitory activity was localized in several peaks, some of which had retention times corresponding to 1,4-benzodiazepine standards. The presence of diazepam in these extracts was confirmed using mass spectroscopy. Both mass spectroscopic and radiometric techniques demonstrated that the concentration of diazepam in brain extracts from encephalopathic rabbits was approximately 4 times greater than control extracts. These findings link the presence of BZ receptor agonists to the development of a neuropathological condition, thereby providing a rational basis for the use of BZ receptor antagonists in the management of HE in man.

Animals↗
PubMed1990

Reversal of the behavioral and electrophysiological abnormalities of an animal model of hepatic encephalopathy by benzodiazepine receptor ligands.

Behavioral and electrophysiological evidence implicating the GABA-benzodiazepine receptor complex in the pathogenesis of hepatic encephalopathy was obtained using an improved rat model of hepatic encephalopathy caused by thioacetamide-induced fulminant hepatic failure. After the administration of thioacetamide together with supportive therapy, acute hepatocellular failure developed in rats as a result of massive hepatocellular necrosis without evidence of renal failure or hypoglycemia. The evolution of hepatic encephalopathy in this model was sufficiently slow to readily permit the staging of the syndrome. Prominent features of the encephalopathy include a marked reduction in open field activity and an abnormal visual evoked response. Both the deficits in spontaneous motor function and visual evoked response abnormalities of rats in stages III to IV hepatic encephalopathy were significantly improved after the administration of the benzodiazepine receptor ligands flumazenil or Ro 15-4513. Doses of flumazenil or Ro 15-4513 that produced these effects in rats with hepatic encephalopathy had no detectable action on either the behavior or the visual evoked responses of normal rats. The ability of benzodiazepine receptor ligands to ameliorate both the behavioral depression and the visual evoked response abnormalities associated with hepatic encephalopathy in the thioacetamide-induced rat model suggest an involvement of the GABA/benzodiazepine receptor complex in the pathogenesis of hepatic encephalopathy. In addition, the similarity of these observations to those in rabbits with hepatic encephalopathy caused by galactosamine-induced fulminant hepatic failure is compatible with the hypothesis that the mechanisms of hepatic encephalopathy in these two distinct models share a common final pathway, the allosteric enhancement of GABAergic tone through the benzodiazepine receptor.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Hepatic encephalopathy, GABA-ergic neurotransmission and benzodiazepine receptor ligands.

Evidence compatible with increased GABAergic tone contributing to the manifestations of hepatic encephalopathy (HE) in animal models of fulminant hepatic failure (FHF) includes: (i) increased resistance to drugs which induce seizures by reducing GABAergic tone; (ii) abnormalities of visual evoked responses (VERs) which resemble those induced by drugs which augment GABAergic tone; (iii) increased sensitivity of CNS neurons to a GABA agonist; and (iv) ameliorations of the encephalopathy induced by a GABA receptor antagonist. Evidence compatible with a benzodiazepine (BZ) receptor ligand with agonist properties contributing to increased GABAergic tone in animal models of FHF includes: (i) abnormalities of VERs which resemble those in BZ agonist-induced coma; (ii) increased sensitivity of CNS neurons to a BZ receptor agonist; (iii) excitation of CNS neurons induced by BZ receptor antagonists; (iv) reversal of the increased sensitivity of CNS neurons to a GABA agonist by a BZ receptor antagonist; (v) presence of a ligand(s) in brain which displaces a radiolabeled ligand from BZ receptors; and (vi) increased affinity of this ligand(s) for BZ receptors in the presence of GABA ("positive GABA shift").

Animals↗
PubMed1990

Brain concentrations of benzodiazepines are elevated in an animal model of hepatic encephalopathy.

Brain extracts from rats with hepatic encephalopathy due to thioacetamide-induced fulminant hepatic failure contained 4- to 6-fold higher concentrations of substances that inhibit radioligand binding to benzodiazepine receptors than corresponding control rat extracts. Both isocratic and gradient-elution HPLC indicated that this inhibitory activity was localized in 3-8 peaks with retention times corresponding to deschlorodiazepam, deschlorolorazepam, lorazepam, oxazepam, diazepam, and N-desmethyldiazepam. The presence of diazepam and N-desmethyldiazepam was confirmed by mass spectroscopy. Both mass spectroscopic and radiometric techniques indicated that the concentrations of N-desmethyldiazepam and diazepam in brain extracts from encephalopathic rats were 2-9 and 5-7 times higher, respectively, than in control brain extracts. While benzodiazepines have been identified previously in mammalian and plant tissues, this report demonstrates that concentrations of these substances are increased in a pathophysiological condition. These findings provide a rational basis for the use of benzodiazepine receptor antagonists in the management of hepatic encephalopathy in humans.

Animals↗
PubMed1990

The involvement of the benzodiazepine receptor in hepatic encephalopathy: evidence for the presence of a benzodiazepine receptor ligand.

The involvement of GABAergic systems in the pathogenesis of HE was supported by electrophysiologic studies of single Purkinje neurons from rabbits with HE which demonstrated the hypersensitivity of these neurons to depression by GABA and BZ receptor agonists. In contrast, these neurons were excited by BZ receptor antagonists. At concentrations which had no effect on neuronal activity, BZ receptor antagonists also reversed the hypersensitivity of HE neurons to depression by muscimol. This combination of neuronal responses is consistent with an increase in the concentration or availability of a ligand for the BZ receptor with agonist properties in the brains of rabbits with HE. Subsequent neurochemical studies support these electrophysiologic observations. Autoradiographic techniques indicated the presence of a reversible inhibitor of [3H]Ro 15-1788 and [3H]flunitrazepam binding to the cerebral and cerebellar cortices of rabbits with HE. The ability of this substance to inhibit [3H]flunitrazepam binding to HE rabbit brain sections was further enhanced in the presence of NaCl and GABA. The autoradiographic studies suggested that the density and affinity of the components of the GABA-BZ receptor complex are unaltered in this animal model of HE. This inference is fully supported by the subsequent studies of radioligand binding to well-washed membrane preparations. Finally, extracts of HE rabbit brains yielded a family of substances with the properties of BZ receptor agonists. These substances may include, but are not limited to, diazepam, oxazepam and desmethyldiazepam, but do not include substances commonly elevated in the plasma and CSF of patients with HE4. The positive identification of these substances awaits confirmation by mass-spectroscopic analysis. However, the precedent for the presence of a family of benzodiazepines in animals that were not administered these drugs has been set. The origin of these substances is a matter of ongoing research. Several studies have shown the presence of benzodiazepines in plant and animal materials. It is possible that these "endogenous" benzodiazepines are the result of contamination of the food chain. A normally functioning liver would capture and metabolize these compounds after their absorption from the gut. This function of the liver would be impaired in liver failure, thus allowing sufficient levels of BZ receptor agonists to accumulate in the CNS, contributing to the pathogenesis of HE. However, studies by DeBlas and coworkers have reported that 1,4 benzodiazepines are present in human brains preserved prior to the commercial use of these compounds. Further, they have found benzodiazepines in cell lines cultured without potential exogenous sources of benzodiazepines.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1990

The GABAA receptor complex in hepatic encephalopathy. Autoradiographic evidence for the presence of elevated levels of a benzodiazepine receptor ligand.

Autoradiographic analysis was used to examine radioligand binding to benzodiazepine (BZ) and GABAA receptors in the brains of rabbits with hepatic encephalopathy (HE). Thin sections of whole brain from normal rabbits and rabbits with HE were mounted on slides and subdivided into two groups. One group was washed before incubation with radioligand, while the second group was not prewashed. [3H]Flunitrazepam binding to BZ receptors was decreased by 22% to 42% (p less than 0.05) in the cerebral cortex, superior and inferior colliculi, and cerebellum of unwashed sections from rabbits with HE compared to all other groups. The binding of [3H]Ro 15-1788 to unwashed sections from rabbits with HE was reduced by a similar degree (18% to 37%, p less than 0.05) in the cerebral cortex, hippocampus, superior colliculus, and cerebellar cortex. Incubation of sections with the GABA-mimetic muscimol and NaCl produced an additional decrease in [3H]flunitrazepam binding to the cortex and hippocampus (25% to 31%, p less than 0.05) in unwashed HE rabbit brain, but increased radioligand binding (27% to 71%, p less than 0.05) to several regions in control rabbits. No changes in radioligand binding to either GABAA or peripheral benzodiazepine receptors was observed between HE and control rabbit sections. These findings are consistent with previous electrophysiologic and neurochemical observations indicating no significant changes in either the function or density of GABAA or BZ receptors in this model of HE. Further, they indicate that a reversible BZ receptor ligand with agonist properties is present in the brain in HE. This substance may contribute to the enhancement of GABAergic tone observed in this syndrome.

Animals↗
PubMed1989

NIH conference. The gamma-aminobutyric acid A (GABAA) receptor complex and hepatic encephalopathy. Some recent advances.

Increased neural inhibition appears to be an important component of the syndrome of hepatic encephalopathy. The pathways subserved by the gamma-aminobutyric acid (GABA)-benzodiazepine receptor complex are the principal inhibitory systems in the mammalian brain. Hyperpolarization of neural membranes is accomplished by an increase in transmembrane chloride flux through a GABA-gated chloride channel in the complex. The opening of the chloride channel is induced by the binding of GABA to its receptors, and it is potentiated by barbiturates or benzodiazepines that act at distinct recognition sites on the complex. Involvement of the GABA neurotransmitter system in hepatic encephalopathy is suggested by several findings in animal models of fulminant hepatic failure. For example, hepatic encephalopathy resembles encephalopathies induced by drugs (including benzodiazepines) that potentiate GABAergic neurotransmission. In addition, neurons from animals with hepatic encephalopathy show increased sensitivity to benzodiazepine and GABA receptor agonists. Moreover, these neurons are excited by benzodiazepine receptor antagonists at concentrations that do not affect control neurons. Also, elevated levels of a substance that inhibits radioligand binding to benzodiazepine receptors have been found in cerebrospinal fluid from animals with hepatic encephalopathy. Furthermore, manifestations of hepatic encephalopathy can be ameliorated by benzodiazepine receptor antagonists. The relevance of these findings to hepatic encephalopathy in human beings is supported by clinical observations showing that a benzodiazepine receptor antagonist can lessen the degree of hepatic encephalopathy. These findings suggest that an endogenous substance with benzodiazepine-like properties contributes to the neuropsychiatric manifestations of hepatic encephalopathy by augmenting GABAergic neurotransmission.

Action Potentials↗
PubMed1989

GABAA receptor complex in an experimental model of hepatic encephalopathy: evidence for elevated levels of an endogenous benzodiazepine receptor ligand.

The involvement of the gamma-aminobutyric acidA (GABAA) receptor complex in the pathogenesis of hepatic encephalopathy was examined in thioacetamide-treated rats with fulminant hepatic failure. Partially purified extracts from encephalopathic rat brain were approximately three times more potent in inhibiting [3H]Ro 15-1788 binding to benzodiazepine receptors than identically prepared extracts from control rats. High levels of inhibitory activity were also found in extracts of plasma, heart, and liver from thioacetamide-treated rats. The inhibition of [3H]Ro 15-1788 binding by brain extracts appeared to be competitive and reversible and was unaffected by treatment with either proteolytic enzymes or boiling. Further, GABA significantly enhanced the potency of these extracts in inhibiting [3H]flunitrazepam binding. In contrast, no differences were found in radioligand binding to the constituent recognition sites of the GABAA receptor complex in well-washed brain membranes prepared from control and encephalopathic animals. These findings suggest that the recognition-site qualities of the constituent proteins of the GABAA receptor complex are unchanged in an experimental model of hepatic encephalopathy. However, significant elevations in the level of a substance or substances with neurochemical properties characteristic of a benzodiazepine receptor agonist may contribute to the electrophysiological and behavioral manifestations of hepatic encephalopathy.

Animals↗
PubMed1989

Characterization of the effects of AHN 086, an irreversible ligand of "peripheral" benzodiazepine receptors, on contraction in guinea-pig atrial and ileal longitudinal smooth muscle.

The effects of AHN 086 and its reversibly acting structural analogue Ro 5-4864 were studied in the spontaneously beating guinea-pig atria and field-stimulated guinea-pig ileal longitudinal smooth muscle in the presence and absence of dihydropyridine calcium channel modulators. The treatment of guinea-pig atria with AHN 086 followed by extensive washing did not alter contraction. However, AHN 086 (0.5 microM) potentiated (88%) the positive inotropic responses by BAY K 8644, an effect that was not reversed by extensive washing of the tissue. Higher concentrations of AHN 086 (greater than 2 microM) irreversibly inhibited the intropic, but not the chronotropic responses to BAY K 8644, nifedipine, and isoproterenol. Ro 5-4864 (10 microM) produced a reversible enhancement of the inotropic responses and block of the chronotropic responses to BAY K 8644. In guinea-pig ileal longitudinal smooth muscle, both AHN 086 and Ro 5-4864 reversibly inhibited field-stimulated contractions. Neither Ro 5-4864 nor AHN 086 affected the ability of nifedipine to inhibit field-stimulated contractions of ileal longitudinal smooth muscle. Treatment of intact atrial with 5 microM AHN 086 followed by extensive washing resulted in a significant inhibition (30-50%) of [3H]Ro 5-4864 binding to peripheral benzodiazepine receptors and of [3H]nitrendipine binding to voltage-operated calcium channels, but did not affect [3H]dihydroalprenolol binding to beta-adrenergic receptors on atrial membranes. The same treatment applied to intact ileal longitudinal smooth muscle affected neither [3H] (-)-quinuclidinyl benzilate binding to muscarine receptors nor [3H]nitrendipine binding, but did result in a significant inhibition (30-50%) of [3H]Ro 5-4864 binding to ileal longitudinal smooth muscle membranes.(ABSTRACT TRUNCATED AT 250 WORDS)

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1989

Electrophysiological actions of Ro5-4864 on cerebellar Purkinje neurons: evidence for "peripheral" benzodiazepine receptor-mediated depression.

The effects of Ro 5-4864 (4'-chlorodiazepam; the archetypic peripheral benzodiazepine receptor ligand) were examined on the electrophysiological responses of rat cerebellar Purkinje neurons maintained in vitro. Ro 5-4864 produced a biphasic response (consisting of an increase followed by a decrease in spontaneous firing) in approximately 50% of the neurons studied. The remaining neurons responded to Ro 5-4864 application with decreased spontaneous activity. The EC50 and IC50 values for the excitatory and depressant responses to Ro 5-4864 were 490 and 450 nM, respectively. Preincubation with PK 11195 [N-methyl-N-(methyl-1-propyl)chloro-2-phenyl-1-isoquinoline-3-carboxamid e; a peripheral benzodiazepine receptor antagonist] reduced the potency of Ro 5-4864 to inhibit cell firing in a competitive fashion, but did not alter Ro 5-4864-elicited excitations. A similar effect was observed with the monocarboxylic acid anion transport inhibitor UK 5099 [alpha-cyano-beta-(1-phenylindol-3-yl)acrylate]. In contrast, the increases in cell firing elicited by t-butylbicyclophosphorothionate (a GABA-gated chloride channel blocker) were enhanced 6-fold by coperfusion with both Ro 5-4864 and PK 11195. These findings suggest that the Ro 5-4864 induced depressions of Purkinje neuron spontaneous activity is mediated by peripheral benzodiazepine receptors, whereas the excitation may result from modulation of the gamma-aminobutyric acid-gated chloride ionophore.

Animals↗
PubMed1988

Modulation of neurotransmitter metabolism by dihydropyridine calcium channel ligands in mouse brain.

The regional concentrations of dopamine, serotonin, dihydroxyphenylacetic acid, homovanillic acid and 5-hydroxyindole acetic acid were measured in mouse brain following administration of the dihydropyridine calcium channel activator BAY K 8644, and antagonist, nifedipine. BAY K 8644 (1-8 mg/kg) produced dose- and time-dependent increases in dihydroxyphenylacetic acid, homovanillic acid and 5-hydroxyindoleacetic acid concentrations in the caudate, without altering dopamine and serotonin levels. No changes in 5-hydroxyindoleacetic acid concentration were observed in the raphe nuclei, hypothalamus, hippocampus and frontal cortex. Nifedipine (4 mg/kg) blocked BAY K 8644- (2 mg/kg) elicited increases in dihydroxyphenylacetic acid in the caudate. Furthermore, a higher dose of nifedipine (8 mg/kg) decreased dihydroxyphenylacetic acid and homovanillic acid, but did not affect dopamine, serotonin or 5-hydroxyindoleacetic acid concentrations, while a lower dose of nifedipine (2 mg/kg) significantly increased serotonin, 5-hydroxyindoleacetic acid and homovanillic acid, but did not affect dopamine and dihydroxyphenylacetic acid concentrations. The findings that both BAY K 8644 and nifedipine affect neurotransmitter metabolism in vivo in a dose-, time- and brain region-dependent manner, suggest that high-affinity dihydropyridine calcium channel binding sites play an important role in regulating neurotransmitter turnover in the central nervous system.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1988

Regulation of renal peripheral benzodiazepine receptors by anion transport inhibitors.

The in vitro and in vivo regulation of [3H]Ro 5-4864 binding to peripheral benzodiazepine receptors (PBR) by ion transport/exchange inhibitors was studied in the kidney. The potencies of 9-anthroic acid, furosemide, bumetanide, hydrochlorothiazide and SITS as inhibitors of [3H]Ro 5-4864 binding to renal membranes were consistent with their actions as anion transport inhibitors (Ki approximately equal to 30 - 130 microM). In contrast, spironolactone, amiloride, acetazolamide, and ouabain were less potent (Ki = 100-1000 microM). Administration of furosemide to rats for five days resulted in a profound diuresis (approximately equal to 350% increase in urine volume) accompanied by a significant increase in PBR density (43%) that was apparent by the fifth day of treatment. Administration of hydrochlorothiazide or Ro 5-4864 for five days also caused diuresis and increased renal PBR density. Both the diuresis and increased density of PBR produced by Ro 5-4864 were blocked by coadministration of PK 11195, which alone had no effect on either PBR density or urine volume. The equilibrium binding constants of [3H]Ro 5-4864 to cardiac membranes were unaffected by administration of any of these drugs. These findings suggest that renal PBR may be selectively modulated in vivo and in vitro by administration of ion transport/exchange inhibitors.

4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfo↗