一些植物成分对实验肿瘤的作用

观察了18个植物成分对S180、Lewis肺癌、B16黑色素瘤、Ehrlich腹水癌、白血病P388、L1210和L615等小鼠肿瘤的疗效。以白血病P388和L1210最为敏感,L615最不敏感。此外,试验了高三尖杉酯碱、美登素、羟基喜树碱和长春新碱对Friend白血病的疗效,仅高三尖杉醋碱有明显疗效。部分样品还观察了对~3H标记的前体参入肿瘤细胞核酸和蛋白质的影响。     

Effect of dotarizine on K+-stimulated [3H]-serotonin and [3H]-acetylcholine release from rat hippocampus

• 1.1. The effect of the diphenylmethyl-piperazine derivative dotarizine on K⁺-stimulated release of [³H]serotonin ([³H]5-HT) and [³H]acethylcholine ([³H]Ach) in rat hippocampal slices was studied.
• 2.2. Dotarizine at a concentration of 10⁻⁶ M significantly decreased the basal [³H]5-HT release and, at a concentration of 10⁻⁵ M, it significantly decreased the K⁺-stimulated [³H]5-HT release compared to vehicle controls.
• 3.3. Dotarizine, at a concentration of 5 × 10⁻⁷ M, significantly increased both basal and K⁺-stimulated [³H]Ach release. At higher concentrations (10⁻⁶ and 2 × 10⁻⁶ M), dotarizine did not change the basal release but significantly increased the K⁺-stimulated [³H]Ach release. The effect of dotarizine on K⁺-stimulated [³H]Ach release decreased with increasing dotarizine concentrations.
• 4.4. It is speculated that, in addition to its Ca²⁺ antagonistic activity, dotarizine exerts an antagonistic effect on the presynaptic 5-HT autoreceptors, which could account for the facilitation of [³H]Ach release.

     

Effect of chronic ethanol and sucrose ingestion on liver polysomal poly(A)mRNA content and incorporation of [5-3H]uridine into mRNA

Mice fed a combination of 10 per cent (v/v) ethanol and 5 per cent (w/v) sucrose for 5 months showed a 2-fold increase in the amount of [5-³H]uridine label that was incorporated into putative mRNA in the polysomes of the liver. Part of the increase was due to a change in the total amount of UTP present in the cell, although the uptake and processing of [5-³H]UTP were not altered. When corrected for UTP pool size variation, ethanol-sucrose-treated mice still incorporated 1.5-fold more [5-³H]uridine-labeled RNA into polysomes than controls. Poly(A⁺)mRNA content was 1.2 times greater in ethanol-sucrose-treated mice, and [5-³H]poly(U) hybridization t poly(A) tracts may be 1.5 times longer in ethanol-sucrose-treated mice than in controls. [Poly(A)mRNA is the same as poly(A⁺)mRNA]. The proportion of newly labeled poly(A^?)mRNA declined in ethanol-sucrose-treated mice compared to controls. The results indicate that ethanol-sucrose treatment may cause an increase in the amount of poly(A⁺)mRNA that has longer poly(A) tracts and a concomitant decline in the amount of [5-³H]uridine label incorporated into poly(A^?)mRNA. A decline in protein synthesis could not be explained by a lack of mRNA in ethanol-sucrose fed mice.     

Effect of Sequence of Administration on the Pharmacokinetic Interaction between the Anticholinergic Drug Biperiden and [3H]Quinuclidinyl Benzylate or [3H]N-Methylscopolamine in Rats

In rats the pharmacokinetic interactions between the anticholinergic drug biperiden and [³H]quinuclidinyl benzylate ([³H]QNB) or [³H]N-methylscopolamine ([³H]NMS) is affected by the sequence in which the drugs are administered. Drug concentrations in various tissues were determined after intravenous administration of [³H]QNB or [³H]NMS (325 ng kg^?1). Biperiden (6.4 mg kg^?1) was administered either 5 min before, concomitantly with or 20 min after injection of [³H]QNB or [³H]NMS. When biperiden was administered concomitantly with or before [³H]QNB, distribution of [³H]QNB among the regions of the brain and other tissues was reduced; at 4 h the ratio of the distribution of [³H]QNB for experimental animals to that for control animals ranged from 0.15 to 0.9. When biperiden was administered after [³H]QNB, the distribution of [³H]QNB in the brain and other tissues was significantly higher than for the other two treatments (P < 0.01). However, for [³H]NMS the sequence of administration had no effect on the distribution of the drug in the brain and other tissues except for the kidney. In-vitro, in crude synaptosomal membranes, the amount of [³H]QNB at 2 h relative to the control concentration at equilibrium was 87% when biperiden was added before [³H]QNB and 56% when biperiden was added after [³H]QNB. In both instances the concentration of [³H]NMS reached equilibrium within 30 min. These findings suggest that the difference between the rate constant of association and dissociation at the possible site of action gives rise to the effect of the sequence of administration on the pharmacokinetic interaction.     

3H]Dihydroergocryptine binding to alpha-adrenergic receptors of human platelets. A reassessment using the selective radioligands [3H]prazosin, [3H]yohimbine, and [3H]rauwolscine

Which subtype(s) of the alpha-adrenergic receptor occurs on human platelets? Studies of platelet responsiveness to adrenergic compounds and indirect radioligand binding studies addressing this question have yielded contradictory conclusions. These binding studies employed the ligand [³H]dihydroergocryptine ([³H]DHE), an alpha-adrenergic antagonist that does not select between alpha₁- and alpha₂-adrenergic receptors and that also binds to other receptor types in some tissues. To determine the subtype of the platelet alpha-adrenergic receptor, we have examined the binding to intact human platelets of [³H]prazosin (alpha₁-selective), [³H]yohimbine (alpha₂-selective), and [³H]rauwolscine (alpha₂-selective), and we have compared the binding of these selective radioligands with that of [³H]DHE. [³H]Yohimbine and [³H]rauwolscine both bound with high affinity (K_D = 2.7 and 4.6 nM, respectively) to an equal number and a single class (Hill coefficient ～1.0) of sites (～300 per platelet), but [³H]yohimbine yielded lower nonspecific binding than did [³H]rauwolscine. In paired experiments, [³H]DHE bound to 1.5 times as many (phentolamine-displaceable) sites as did [³H]yohimibine or [³H]rauwolscine. Unlabeled vohimbine and epinephrine competed for fewer [³H]DHE binding sites than did phentolamine. Thus, in addition to binding to the alpha₂-adrenergic receptors identified by [³H]yohimbine and [³H]rauwolscine, [³H]DHE seems to bind to other sites on human platelets. The nature of these sites is not clear. We found that [³H]prazosin did not identify alpha₁-adrenergic receptors on platelets, and that phenoxybenzamine only inhibited [³H]yohimbine and [³H]DHE binding at higher concentrations than usually observed for alpha₁-adrenergic receptors. We conclude that (1) all alpha-adrenergic sites on human platelets are of the alpha₂ subtype, (2) [³H]DHE may bind to additional, as yet ill-defined, sites in addition to those sites identified by [³H]yohimbine and [³H]rauwolscine, and (3) [³H]yohimbine is the preferred antagonist radioligand for studying the alpha₂-adrenergic receptors on human platelets.     

Subcellular distribution of [3H]amphetamine and [3H]guanethidine and their interaction with adrenergic neurons

The subcellular distribution of [³H]amphetamine and [³H]guanethidine and their interaction with each other and with noradrenaline binding sites have been examined. The ratio p/(p + s) × 100, an indication of affinity for noradrenaline storage particles, for [³H]amphetamine and [³H]guanethidine was 12% and 57% respectively. Protriptyline, a substance which inhibits amine transport mechanism at the level of the cell membrane, i.e. the membrane pump, and reserpine, an agent which impairs incorporation of amines into the storage particles in the adrenergic nerve fibre, inhibited the uptake and storage respectively, of [³H]guanethidine more than that of [³H]amphetamine. Retention of [³H]guanethidine by rat salivary glands was markedly decreased by sympathetic denervation of the glands while that of [³H]amphetamine was not. The results suggest that guanethidine possesses a much higher affinity for noradrenaline binding sites than amphetamine.     

The effect of the nucleoside transport inhibitor dipyridamole on the incorporation of [3H]thymidine in the rat

Dipyridamole is a non-specific inhibitor of nucleoside transport into mammalian cells. It is currently undergoing clinical evaluation in combination with various antimetabolites in an attempt to enhance the activity of these anticancer drugs by blocking the salvage of extracellular nucleosides, an important determinant of their cytotoxicity. In the present study, the effect of i.v. infusions of dipyridamole on [3H]thymidine incorporation into DNA has been examined in the anaesthetized rat. The tissues studied were bone marrow, gastrointestinal tract epithelium and the ascitic form of the Walker carcinosarcoma. Dipyridamole at 10 mg/kg, given over 3 hr, led to plasma levels of less than 5 microM and did not reduce [3H]thymidine incorporation into any of the tissues studied. At 40 mg/kg dipyridamole (plasma levels 10-15 microM) [3H]thymidine incorporation into the DNA of bone marrow and gastrointestinal tract epithelium was reduced to 20-30% of control values. Increasing the dose to 100 mg/kg did not lead to a further suppression of incorporation. Measurement of [3H]thymidine plasma pharmacokinetics and the intracellular distribution of tritium suggested that the inhibition of [3H]thymidine incorporation was due to reduced cellular uptake. In contrast to the effects on normal tissues, even at a lethal dose (200 mg/kg) dipyridamole did not significantly inhibit [3H]thymidine incorporation into Walker tumour cells. The levels of dipyridamole found in the ascitic fluid, at 100 mg/kg approximately half those in plasma, argue against a pharmacokinetic basis for this difference. Dipyridamole was found to bind extensively (97%) to rat plasma proteins, which may explain the discrepancy between the concentrations of dipyridamole required to inhibit nucleoside incorporation in vitro, in serum-free media, and those needed in vivo. From a comparison of the plasma levels of dipyridamole which cause an inhibition of [3H]thymidine incorporation in the rat with those which can be achieved safely in patients, it is concluded that dipyridamole is unlikely to markedly reduce nucleoside salvage in man.     

4-[4″-(2″,2″,6″,6″-四甲基哌啶氮氧自由基)氨基]-4′-去甲表鬼臼毒对L1210细胞系增殖、克隆形成和DNA合成的影响

新合成的鬼臼毒自旋标记衍生物4-(4″-(2″,2″,6″,6″-四甲基哌啶氮氧自由基)氨基)-4′-去甲表鬼臼毒(GP-7)显著抑制体外培养的L1210细胞生长。抑制作用和浓度及处理时间正相关,作用特点和鬼臼乙叉甙(VP-16)相似,24,48hIC_(50)分别为1.51和0.13μmol/L。GP-7和VP-16对L1210细胞软琼脂克隆形成均有抑制作用,且有浓度依赖性,IC_(50)分别为3.29和2.82μmol/L。GP-70.08～100μmol/L对L1210细胞DNA合成抑制率为18.4～80.7％。本文结果表明GP-7体外抗肿瘤作用与VP-16相似。     

Binding characteristics of [3H] guanfacine to rat brain α-adrenoceptors: Comparison with [3H]clonidine

The tritium-labeled α-adrenoceptor agonist and antihypertensive drug guanfacine, N-amidino-2-(2,6-dichlorophenyl)-acetamide (sp. act. 24.2 $\text{Ci}\text{mmole}$) was employed for a direct identification and characterization of α-adrenoceptors in rat brain membranes. Its usefulness as a radioligand was studied in comparison with [³H]clonidine (sp. act. 26.7 $\text{Ci}\text{mmole}$). The nonspecific binding of [³H]guanfacine to rat cerebral membranes was considerably more pronounced than that observed for [³H]clonidine. The specific binding of [³H] guanfacine (0.1–20 nM) and [³H]clonidine (0.1–20 nM) as defined as the excess over blanks containing (?)-norepinephrine (10μM) was saturable. Scatchard analyses of these binding data indicated single populations of binding sites for both ligands. K_D values of 3.9 ([³H]guanfacine) and 3.7 nM ([³H]clonidine) were calculated. Maximal number of specific binding sites amounted to 220 and 195 $\text{fmole}\text{mg}$ protein for [³H]guanfacine and [³H]clonidine, respectively. In case unlabeled guanfacine (1 μM) was used to characterize the specific binding of [³H] guanfacine, K_d value and maximal number of binding sites were about twice as high as determined in the presence of excess (?)-norepinephrine. The rate of association of both radioligands was rapid. Binding reached equilibrium by about 10–15 min of incubation. Half-maximal binding was attained at approximately 1–2 min. The rates of dissociation were biphasic. A rapid and a slow component were identified. The specific binding sites of [³H] guanfacine in rat brain possess the general characteristics of α₂-adrenoceptors. Selective antagonists of α₂-adrenoceptors, like yohimbine and rauwolscine strongly interfered with this binding. However, preferential blocking agents of α₁-adrenoceptors, such as prazosin and corynanthine, were weak competitors. The relative potency of agonists and antagonists in displacing [³H]guanfacine was identical to their effectiveness in competing for [³H]clonidine specific binding sites. It is concluded that [³H]guanfacine labels the same α₂-adrenoceptor population in rat brain as [³H]clonidine. However, [³H]guanfacine seems not as suitable as [³H]clonidine for routine use in the direct identification of α₂-adrenoceptors in view of its relatively high nonspecific binding.     

Reduced [H]quinuclidinyl benzilate binding to muscarinic receptors in disulfoton-tolerant mice

The organophosphate, acetylcholinesterase inhibitor, disulfoton, O,O-diethyl S-[2-(ethylthio)ethyl]phosphorodithioate, was given daily for 2 weeks to male mice at two different dosages. Clinical signs of poisoning disappeared in 5 days after the beginning of the treatment, i.e., the animals developed apparent tolerance to disulfoton toxicity. Tolerant mice were less sensitive to a lethal dose of carbachol and exhibited a decrease of [³H]quinuclidinyl benzilate ([³H]QNB) binding in forebrain, hindbrain, and ileum. Scatchard analysis of saturation experiments revealed a decrease in the density of receptors (B_max) in the disulfoton-treated mice, as compared with controls. No significant changes in affinity were found, except in the ileum. A time-course study showed a good parallelism between the decrease of [³H]QNB binding and the development of tolerance. Twenty-one days after the end of the disulfoton treatment AChE activity was still inhibited, but [³H]QNB binding had returned to normal levels. The recovery of [³H]QNB binding appears to be faster in ileum than in forebrain and hindbrain. These findings indicate that the development of tolerance to chronic organophosphate treatment is, at least partially, due to a reduction in the number of cholinergic receptors.     

Regional in vivo binding of [3H]N-propylnorapomorphine in the mouse brain. Evidence for labelling of central dopamine receptors

Tain vein injections of [³H]N-propylnorapomorphine ([³H]NPA) in male mice resulted in a dose-related accumulation of radioactivity in the following brain regions: striatum (max), olfactory tubercle and cerebellum (min). The specific binding was saturable with increasing concentrations of the drug and stereospecifically displaced by (+)butaclamol. Dopamine agonists (apomorphine, NPA and bromocriptine) and antagonists (spiperone, haloperidol, (+)butaclamol and l-sulpiride) all caused dose-dependent prevention of [³H]NPA binding. Mianserin, phenoxybenzamine and propranolol did not prevent the in vivo [³H]NPA binding suggesting that [³H]NPA binds specifically to dopamine receptors in the striatum and the olfactory tubercle of the mouse.     

Platelet 5-HT uptake sites in depression: three concurrent measures using [3H] imipramine and [3H] paroxetine

Platelet 5-HT uptake sites were measured in 40 depressed patients and 40 controls using [³H] imipramine binding, defined with desmethylimipramine (DMI) and Na⁺ dependence, and [³H] paroxetine binding. In control subjects the B_max of DMI defined [³H] imipramine binding was significantly higher than both Na⁺ dependent [³H] imipramine (by 30%) and [³H] paroxetine binding (by 22%). The B_max of Na⁺ dependent [³H] imipramine and [³H] paroxetine binding did not differ significantly. The K_d of Na⁺ dependent [³H] imipramine binding was significantly lower than the K_d of DMI defined [³H] imipramine binding. The binding of DMI defined and Na⁺ dependent [³H] imipramine and [³H] paroxetine did not differ significantly between depressed patients and controls in the total group, in those depressed patients who had never taken antidepressants or in those depressed patients who had been recently with-drawn from antidepressants. This study provides no support for the view that the number of platelet 5-HT uptake sites are reduced in depression.     

Reversal of the cytotoxicity of 3'-amino-3'-deoxythymidine by pyrimidine deoxyribonucleosides.

Mammalian cell replication is strongly inhibited by 3′-amino-3′deoxythymidine (3′-aminothymidine). This cytotoxieity can be specifically prevented or reversed by pyrimidine 2′-deoxyribonucleosides. The addition of 50 μM 2′-deoxycytidine to L1210 cells treated with 10 μM 3′ the population doubling time from about 38 hr to 17 hr. The control cells doubled every 13 hr. Another cytotoxic effect produced by 3′-aminothymidine is a dose- and time-dependent increase in cell volume. 2′-Deoxycytidine can effectively prevent and reverse this increase. 3′-Aminothymidme appears to be a potent selective inhibitor of DNA synthesis in L1210 cells. The incorporation of [³H]thymidine into DNA was inhibited by 50 per cent at 1 μM 3′-aminothymidine, a concentration which reduced L1210 replication by about 65 per cent. The rate of incorporation of [³H] adenine into DNA, another measure of DNA synthesis, was reduced similarly by 3′-aminothymidine. and 2′-deoxycytidine eliminated this inhibition as well. An effect on RNA or protein synthesis was not detected. The incorporation of [³H] uridine or [³H] adenine into RNA, or of tritiated amino acids into protein, was not reduced by 25 μM 3′-aminothymidine. These results suggest that selective disruption of DNA metabolism may account for the cytotoxicity of 3′-aminothymidine.     

Interaction of dihydroxy-2-aminotetralin derivatives at sites labelled with [3H]clonidine, [3H]prazosin and [3H]spiperone in rat brain membranes

The interactions of 5,6- and 6,7-dihydroxy derivatives of 2-aminotetralin with [³H]clonidine and [³H]clonidine and [³H]prazosin as well as with [³H]spiperone binding sites in rat cerebral cortex membrane preparations were investigated. The hydroxy derivatives of 2-aminotetralin tested showed significant interaction with [³H]clonidine as well as with [³H]spiperone binding sites while for [³H]prazosin binding site these agents appeared virtually inactive. For interaction with [³H]clonidine binding site 6,7-dihydroxy substitutions impart greater potency that 5,6-dihydroxy substitutions and N-alkyl substitutions either make no difference or reduce the affinity of these compounds. N-alkyl substitutions, however, markedly enhance the affinity of 5,6-dihydroxy derivatives for interactions with [³H]spiperone binding site. The results suggest that some hydroxy derivatives of aminotetralin have significant interaction with both central α₂-adrenoceptor and D₂-dopamine receptor systems.     

Transdermal iontophoretic delivery of [3H]GHRP in rats

In this study, we demonstrate transdermal iontophoretic delivery of radiolabeled growth hormone-releasing peptide ([³H]GHRP, [³H]SK&F 110 679) from an iontophoretic patch delivery device in rats. [³H]SK&F 110 679 was adsorbed on a hydrophilic microporous membrane, which was positioned on a support in the device and sealed in place. A silver/silver chloride electrode system was used for iontophoresis and a potential of 4.5 V (rectangular pulse, 40 kHz, 30% duty cycle) was applied using an Advance depolarizing pulse iontophoresis system (ADIS-4030). Current-dependent appearance of [³H]SK&F 110 679 equivalents in blood, bile and urine did not depend on membrane loading between 1.8 and 8 mg adsorbed on the membrane. Blood levels of [³H]SK&F 110 679 equivalents persisted for at least 2 h after the current was turned off, indicative of depot formation in the skin. Fractions of bile and urine were analyzed by reversed-phase high-performance liquid chromatography (HPLC). The radiochemical profiles were dominated by a single species, coeluting with intact [³H]SK&F 110 679. A flux of at least 0.8–1.2 ug/h per cm² was achieved, indicating that, with appropriate optimization of the patch device, therapeutic levels of SK&F 110 679 in man may be attainable by transdermal iontophoresis.     

Uptake and displacement of [3H]dihydroalprenolol, [3H]epinephrine and [3H]clonidine in isolated perfused rabbit lung

Uptake and displacement of three adrenergic receptor ligands, [³H]dihydroalprenolol ([³H]DHA), [³h]epinephrine ([³H]EPI) and [³H]clonidine ([³H]CLON), were examined in isolated rabbit lungs by recirculating perfusion. Removal of [³h]DHA was the most extensive (85% uptake; 6.6 $\text{ml}\text{min}$ clearance), [³H]CLON removal was intermediate (50%; 3.8 $\text{ml}\text{min}$), and [³H]EPI removal was the lowest (33%; 1.2 $\text{ml}\text{min}$). Specific displacement of each radioligand from lung was attempted using several competing agents. Both (?)- and (+)-propranolol equally displaced [³H]DHA from lung. Phentolamine, (?)-phenylephrine and (?)-epinephrine were unable to displace 10 nM [³H]EPI from lung, although the latter two agents did produce concentration-dependent increases in perfusion pressure. High concentrations of (?)-epinephrine, which produced near maximal physiological responses, inconsistently displaced 30–40 nM [³H]EPI from lung. [³H]Clonidine was displaced by unlabeled clonidine at concentrations that caused increases in perfusion pressure. Pretreatment of lungs with either 10 μM phentolamine or phenoxybenzamine did not alter the total amount of [³H]CLON displaced by clonidine, suggesting that [³H]CLON was displaced predominantly from non-specific sites, perhaps preventing detection of [³H]CLON displacement from specific (receptor) sites. Alternatively, these results may be interpreted as inhibition of uptake of each radioligand. Thus, both (?)- and (+)-propranolol interfered with [³H]DHA removal, suggesting a common mechanism for uptake and/or retention for these two β-adrenergic receptor antagonists. Inhibition of ³H]EPI removal was observed only at high concentrations of (?)-epinephrine which indicates that pulmonary removal of epinephrine occurs through a low affinity uptake system. [³H] Clonidine removal was effectively inhibited by the same (μM) concentrations of unlabeled clonidine that produced physiological responses. Neither phentolamine nor phenoxybenzamine was able to interfere with pulmonary removal of [³H]CLON. Therefore, uptake and displacement of these adrenergic receptor radioligands showed no correlation with pharmacological effects produced by these agents in isolated perfused rabbit lung. The results are more closely associated with inhibition of removal and/or non-specific retention of the radioligands examined.     

Pentobarbital differentially inhibits N-methyl-d-aspartate and kainate-stimulated [3H]noradrenaline overflow in rat cortical slices

• 1.1. This study examined the ability of pentobarbital to inhibit NMDA and kainate-stimulated [³H]noradrenaline ([³H]NA) overflow in rat brain cortical slices.
• 2.2. Pentobarbital inhibited NMDA-evoked [³H]NA overflow at 100 μM and greater and inhibited kainate-evoked [³H]NA overflow at 10 μM and greater.
• 3.3. The ability of pentobarbital to inhibit concentration-response curves for NMDA and kainate-evoked overflow of [³H]NA were also examined. Pentobarbital (300 μM) caused a 20% reduction in NMDA and a 50% reduction in kainate-induced maximal responses.

     

Effect of pyrethroids on [3H]kainic acid binding to mouse forebrain membranes

The effect of the pyrethroid insecticides, decamethrin, cis-permethrin, and trans-permethrin, was examined on the in vitro specific binding of [³H]kainic acid ([³H]KA) to receptor sites in mouse forebrain homogenates. All three pyrethroids gave rise to dose-dependent decreases in levels of specific binding. Decamethrin was the most potent in displacing bound [³H]KA giving rise to significant decreases at decamethrin concentrations of 10^?7m and above. Intracere-broventricular injections of the pyrethroids into unanesthetized mice gave rise to neurotoxic symptoms including hyperactivity, tremor, and tonic seizures. The order of potency of the three compounds in causing these symptoms of toxicity (decamethrin >cis-permethrin >trans-permethrin) was found to be the same as their order of potency in displacing bound [³H]KA from binding sites in the mouse brain. These preliminary results suggest that the neurotoxic actions of pyrethroids in mammals may be at least partially mediated via interactions with a kainic acid binding site.     

Pharmacologic characterization of [3H]dopamine and [3H]spiperone binding in mouse cerebellum

• 1.1. [³H]Dopamine and [³H]spiperone binding to cerebellar homogenates was characterized utilizing dopaminergic agonists, antagonists and non-dopaminergic drugs.
• 2.2. The [³H]DA binding to low affinity binding sites reveals a heterogenous population consisting of dopaminergic as well as serotonergic and noradrenergic sites. However, the high affinity binding of [³H]DA reflects dopaminergic sites, although a small contribution of serotonergic and noradrenergic binding sites cannot be excluded.
• 3.3. [³H]Spiperone also labels a heterogenous population of binding sites which, however, are mainly dopaminergic.

     

Light-dark differences in [3H]-paroxetine binding to rabbit platelet membranes

Summary [³H]-Paroxetine binding to rabbit blood platelet membranes from samples obtained under light and dark conditions was examined. Animals were kept on a 14 h light (L) — 10 h dark (D) schedule and blood samples were collected at L + 7 and D + 5 h. Significant differences were found for B _max values of [³H]-paroxetine binding, with low B _max values during the light period and high B _max values during the dark period. The K _d values were not significantly different. These results confirm previous observations on light-dark differences of [³H]-imipramine binding in rabbit blood platelets suggesting the existence of a circadian rhythm for the 5-HT transporter complex.Send offprint requests to S. Z. Langer at the above address