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PubMed1993

The use of sodium sulphide-fixed brain tissue for immunocytochemical staining of activated microglia and reactive astrocytes.

The use of sodium sulphide-perfused material for the immunocytochemical demonstration of microglia and astrocytes is described. An intracerebroventricular injection of kainic acid (KA) was used to induce neuronal degeneration and subsequent axonal sprouting in the hippocampus. Animals under deep anaesthesia were killed by perfusion with either 4% paraformaldehyde alone or with 1% sodium sulphide followed by 4% paraformaldehyde solution. Microglial cells were identified with OX-42, a monoclonal antibody towards CR3 complement receptors, and astrocytes with a polyclonal antibody to glial fibrillary acidic protein (GFAP). The present study reveals a marked enhancement in the immunoreactivity of activated microglial cells in sodium sulphide perfused tissues compared to those observed in tissues fixed in paraformaldehyde alone. GFAP immunoreactivity of the astrocytes was not compromised by the use of sodium sulphide. The results clearly show the suitability of sodium sulphide perfused tissues for immunocytochemical procedures and should provide a useful tool for investigation of the role of neuroglial cells in axonal sprouting.

Animals↗
PubMed1995

Expression of a cytochrome P450 gene family in maize.

Maize seedlings, like seedlings of many other plants, are rich in cytochrome P450 (P450) enzyme activity. Four P450 genes (CYPzm1-4), isolated from a seedling-specific cDNA library, are characterized by a transient and seedling-specific expression pattern. The maximum steady state mRNA levels are reached at 3 days in root and at 7 days in shoot tissue, respectively. All four genes belong to one gene family and are closely related to the CYP71 family of plant P450 genes, which includes the enzymes of the ripening avocado fruit (CYP71A1) and eggplant hypocotyls (CYP71A2, A3, A4). The expression of these related P450 genes in monocot and dicot plants indicates that these enzymes play a significant role in plants; however, the in vivo enzyme functions are unknown. The divergence of the four members of the maize gene family is sufficiently high to account for different substrate and/or reaction specificity. Although the general expression pattern of the four genes is identical, the maximum steady-state mRNA levels vary in different maize lines. In situ hybridisation reveals the highest mRNA levels in the coleoptile, the first developed leaflets, the ground tissue of the nodular complex, and in the cortex and pith of the region of cell division in the root. The mapping of the maize CYPzm genes shows that, as in animals, P450 genes of the same family can be clustered. The presence of the CYPzm gene cluster in maize argues for generation of distinct plant P450 gene families by gene duplication.

Amino Acid Sequence↗
PubMed1995

Bisbenzimide: a fluorescent counterstain for tissue autoradiography.

Interpretation of the data from experiments using autoradiography (e.g. using in situ hybridization histochemistry, receptor binding, neuronal tract-tracing etc.) is aided when the autoradiographic grains can be seen in the context of cellular boundaries. Studies making use of autoradiography in the central nervous system have sometimes used tinctorial stains, such as cresyl violet, as counterstains to visualize the labeling. Tinctorial stains are excellent Nissl stains however, under bright-field illumination such dyes tend to obscure autoradiographic grains. In addition, dark-field illumination provides a common means of visualizing autoradiographic grains but tictorial stains are not optimally visible under these conditions. In an effort to find a counterstain that would be compatible with dark-field illumination, we have investigated the use of fluorescent dyes. Of the fluorescent dyes tested, bisbenzimide (Hoechst 33258) in pH 2.0 buffer was found to be optimal. Bisbenzimide counterstaining gave good resolution of cellular boundaries and appeared not to interfere with the ability to visualize autoradiographic grains. Furthermore, the illumination of bisbenzimide and of the autoradiographic grains could be controlled independently, making it easy to visualize or photograph the bisbenzimide Nissl staining and the autoradiographic grains simultaneously. Thus, bisbenzimide is well suited for use as a fluorescent counterstain in autoradiographic studies.

Animals↗
PubMed1985

A new in vivo staining method, cresyl violet staining, for fiberoptic magnified observation of carcinoma of the gastric mucosa.

A polypoid gastric mucosal lesion with a flat portion was observed by a fiberoptic magnifying endoscope with a new in vivo staining method, cresyl violet staining. The fine surface structure of this lesion showed a characteristic "ruined sulciform pattern" suggesting papillary carcinoma histologically. Successful application of the findings of dissecting microscopy to clinical magnifying endoscopy by means of this new staining material indicates the possibility of diagnosing gastric mucosal carcinomas with much more accuracy.

Benzoxazines↗
PubMedDate not supplied

Lectin histochemistry of the rat brain following thioacetamide-induced hepatic failure.

Biotinyl derivatives of several lectins were used to study the localization of glycoconjugates in the cerebral microcapillaries and various brains of rats given at 24-h intervals two i.p. administrations of a hepatotoxin-thioacetamide (TAA) and examined 21 d posttreatment. At this time, the rats were asymptomatic with regard to hepatic encephalopathy but showed specific and selective changes in the blood-brain-barrier (BBB) transport of basic amino acid, but no BBB damage, and region-specific neuronal injury in the hippocampus and neocortex. The lectins tested recognized the following sugar residues: beta-D-galactosyl (Ricinus communis agglutinin [RCA-1]); N-acetyl-glucosaminyl and N-acetyl-neuraminic acid (wheat-germ agglutinin [WGA]); N-acetyl-D-galactosaminyl (Helix pomatia agglutinin [HPA]); beta-D-galactosyl and D-galactosyl neuraminic acid (peanut agglutinin [PNA]), and alpha-D-galactosyl and alpha-D-mannosyl (concanavalin A [Con A]). The treatment markedly decreased the binding to the cerebromicrovascular network of the hippocampus and neocortex of RCA-1 and WGA. The binding of these two lectins to their complementary monosaccharide residues appears to reflect subtle changes in BBB function, with a detection threshold below the conventional BBB permeability tests. The changes in the binding of the other two lectins: an increase of HPA binding and a decrease of Con A binding, confined to neocortical neurons and pyramidal cells of hippocampus injured by TAA treatment.

Animals↗
PubMed2005

Effects of WIN 55,212-2 on I(K) current in cultured trigeminal ganglion neurons of rat.

To investigate the effects of WIN 55,212-2 on I(K) in cultured rat trigeminal ganglion (TG) neurons, whole-cell patch clamp techniques were used to record the I(K) before and after WIN 55,212-2 perfusion at different concentrations. 30 micromol/L WIN 55,212-2 markedly (35.7% +/- 7.3%, P < 0.01, n = 8) inhibited I(K) currents, and the currents were partially recovered after washing. 30 micromol/L WIN 55,212-2 also induced a significant depolarizing shift in conductance-voltage parameters (control: V0.5 = 10.43 +/- 4.25 mV, k = 16.27 +/- 3.86; WIN 55,212-2: V0.5 = 24.71 +/- 3.91 mV, k =16.69 +/- 2.75; n = 8, P < 0.01 for V0.5). 0.01 micromol/L WIN 55,212-2 slightly (27.0% +/- 7. 9%, P < 0.05, n = 7) increased I(K) currents, but had no significant change in conductance voltage parameters (control: V0.5 =10.74 +/- 5.27 mV, k = 17.33 +/- 2.96; WIN 55,212-2: V0.5 = 11.06 +/- 2.05 mV, k = 19.69 +/- 6.60; n = 7, P > 0.05 for V0.5 and k). These results suggested that WIN 55,212-2 has dual action, which might be through different receptors.

Animals↗
PubMed1999

Effects of placing micro-implants of melatonin in striatum on oxidative stress and neuronal damage mediated by N-methyl-D-aspartate (NMDA) and non-NMDA receptors.

Overstimulation of both kainate (KA) and N-methyl-D-aspartate (NMDA) receptors has been reported to induce excitatoxicity which can be characterized by neuronal damage and formation of reactive oxygen free radicals. Neuroprotective effect of melatonin against KA-induced excitotoxicity have been documented in vitro and in vivo. It is, however, not clear whether melatonin is also neuroprotective against excitotoxicity mediated by NMDA receptors. In the present work, we tested the in vivo protective effects of striatally infused melatonin against the oxidative stress and neuronal damage induced by the injection of KA and NMDA receptors into the rat striatum. Melatonin implants consisting of 22-gauge stainless-steel cannule with melatonin fused inside the tip were placed bilaterally in the rat brain one week prior to intrastriatal injection of glutamate receptor subtype agonists. Melatonin showed protective effects against the elevation of lipid peroxidation induced by either KA or NMDA and recovered Cu,Zn-superoxide dismutase activities reduced by both KA and NMDA into the control level. Melatonin also clearly blocked both KA- and NMDA-receptor mediated neuronal damage assessed by the determination of choline acetyltransferase activity in striatal homogenages and by microscopic observation of rat brain section stained with cresyl violet. The protective effects of melatonin are comparable to those of DNQX and MK801 which are the KA- and NMDA-receptor antagonist, respectively. It is suggested that melatonin could protect against striatal oxidative damages mediated by glutamate receptors, both non-NMDA and NMDA receptors.

Animals↗
PubMed1991

Morphometric study on the CH4 of the nucleus basalis of Meynert in Alzheimer's disease.

Ch4 neurons were studied morphometrically in three normal controls and three patients with Alzheimer's disease (AD). Two series of preparations stained with cresyl violet and with the indirect immunoperoxidase method using a monoclonal antibody to acetylcholinesterase (AChE) counterstained with cresyl violet were morphometrically analyzed. The cholinergic neurons were identified as positive reaction products of AChE in the perikarya. The cross-sectional area of all the Ch4 neurons with clearly visible nucleoli in one preparation was measured using a computer imaging system. Evaluation of these data provided a mean value of the cross-sectional neuronal area (CNA), number of neurons, standard deviation of the CNA and coefficient of variation of the cholinergic and noncholinergic neurons. The cholinergic neurons were decreased in number but showed hypertrophy in the early stage of AD, and they gradually became atrophic in the advanced stage. The noncholinergic neurons showed only atrophy without definite neuronal cell depletion. These findings indicate that cholinergic neurons have a plasticity and remodeling property against the AD process and suggest that hypertrophy of the cholinergic neurons in the Ch4 is the result of the effect of neurotrophic factors.

Acetylcholinesterase↗
PubMedDate not supplied

Pharmacokinetic study in rats after single intravenous and oral administrations of [14C]-ITF-296.

Pharmacokinetics of [14C]-ITF-296 and its metabolites, ITF-1124 and ITF-1577, were studied in rats after a single intravenous (2.5 mg/kg) and oral (10 mg/kg) administration. Radioactivity was measured by LSC while unchanged drug and its metabolites in plasma were assayed by an HPLC-UV method. The absorption of [14C]-ITF-296 after oral administration is practically complete. Elimination of radioactivity occurs mainly in urine (higher than 80%) and the recovery of the dose (higher than 95%) takes place up to 96 h after both treatments. Both by i.v. and p.o. route the results show that the radioactivity is largely excreted in the bile and reabsorbed in the intestine. The tissue distribution study indicates that there is no accumulation or localization of radioactivity in the major organs or blood and no radioactivity levels are found 96 h after either treatment. In addition, whole body autoradiography confirms the tissue distribution pattern, showing no differences between albino and pigmented rats.

Administration, Oral↗
PubMedDate not supplied

Pharmacokinetic study in dogs and monkeys after single intravenous and oral administrations of [14C]-ITF-296.

Pharmacokinetics of [14C]-ITF-296 and its metabolites, ITF-1124 and ITF-1577, were studied in dogs and monkeys after a single intravenous (2.5 mg/kg) and oral (10 mg/kg) administration. Radioactivity was measured by LSC while unchanged drug and its metabolites in plasma were assayed by an HPLC-UV method. The absorption of [14C]-ITF-296 after oral administration is practically complete both in dogs and in monkeys. The determination of unchanged drug and its metabolites shows quite a similar profile in dogs and monkeys for ITF-296 and ITF-1124 and a different time-course for ITF-1577. Elimination of radioactivity occurs mainly in urine (namely 70-80%) for both species and the recovery of the dose (higher than 90%) takes place up to 96 h after both treatments.

Absorption↗
PubMed1999

Defaecation, intestinal fluid accumulation and motility in rodents: implications of cannabinoid CB1 receptors.

We have studied the effect of SR141716A (0.1-5 mg/kg, i.p.), a cannabinoid CB, receptor antagonist, and WIN (0.1-5 mg/kg, i.p.), a cannabinoid receptor agonist, on acute defaecation and gastrointestinal transit in mice and on intraluminal fluid accumulation in the rat small intestine. SR141716A increased while WIN 55,212-2 decreased defaecation, gastrointestinal transit and fluid accumulation. A per se non-effective dose of SR141716A (0.3 mg/kg) counteracted the inhibitory effect of WIN 55,212-2 (1 mg/kg) on gastrointestinal functions studied. The effect of SR 141716 on both intestinal fluid accumulation in rats and gastrointestinal transit in mice was inhibited by atropine (1 mg/kg, i.p.), but not by hexamethonium (1 mg/kg, s.c.), SR140333 (20 microg/kg, i.p.) or SR48968 (20 microg/kg, i.p.), antagonists of NK1 and NK2 receptors, respectively. These results suggest that intestinal fluid accumulation and motility are inhibited by endogenous cannabinoid(s) acting at the cannabinoid CB1 receptors. This effect may be mediated by mechanisms involving muscarinic cholinoceptors.

Animals↗
PubMed1999

Cannabinoid CB1 receptor-mediated inhibition of NMDA- and kainate-stimulated noradrenaline and dopamine release in the brain.

Guinea-pig hippocampal slices preincubated with [3H]noradrenaline were superfused with medium containing desipramine and rauwolscine and rat striatal slices preincubated with [3H]dopamine were superfused with medium containing nomifensine; the effect of cannabinoid receptor ligands on tritium overflow stimulated by NMDA or kainate was examined. Furthermore, the affinity of the drugs for cannabinoid CB1 receptors was determined in rat brain cortex membranes using [3H]SR 141716. In guinea-pig hippocampal slices preincubated with [3H]noradrenaline, tritium overflow stimulated by NMDA 100 microM and 1000 microM and by kainate 1000 microM was inhibited by the cannabinoid receptor agonists CP-55,940 and/or WIN 55,212-2. The CB1 receptor antagonist SR 141716 increased the NMDA (1000 microM)-stimulated tritium overflow but did not affect tritium overflow stimulated by NMDA 100 microM or kainate 1000 microM. The inhibitory effect of WIN 55,212-2 on the NMDA (100 microM)- and kainate (1000 microM)-evoked tritium overflow was antagonized by SR 141716. In rat striatal slices preincubated with [3H]dopamine, WIN 55,212-2 inhibited the NMDA (1000 microM)-stimulated tritium overflow. SR 141716, which, by itself, did not affect tritium overflow, counteracted the inhibitory effect of WIN 55,212-2. [3H]SR 141716 binding to rat cortical membranes was inhibited by SR 141716, CP-55,940 and WIN 55,212-2 (pKi 8.53, 7.34 and 5.93, respectively) but not affected by desipramine, rauwolscine and nomifensine (pKi < 5). In conclusion, activation of CB1 receptors inhibits the NMDA- and kainate-stimulated noradrenaline release in guinea-pig hippocampus and the NMDA-stimulated dopamine release in rat striatum. The explanation for the facilitatory effect of SR 141716 might be that it acts as an inverse agonist at CB1 receptors or that these receptors are activated by endogenous cannabinoids.

Animals↗
PubMed2005

[Rashes in HIV-infected patients undergoing therapy with nevirapine or efavirenz].

Efavirenz and nevirapine are frequently used drugs in antiretroviral therapy. Rashes are common side effects of these drugs. In this study, we examined the characteristics of efavirenz- and nevirapine-associated rashes. This prospective nonrandomized multicenter study included 662 HIV-infected patients (efavirenz: 325, nevirapine: 337) to determine incidence, duration, cross-reactivity, and outcome upon reexposure. Of the treated patients, 4.5% (n=30) developed rashes (nevirapine: 2.4% and efavirenz: 6.4%). In four patients treatment was not interrupted. Three patients were re-exposed to the initial drug without any side effects. Therapy with nevirapine or efavirenz does not have to be interrupted if rashes exhibit no blistering, mucosal manifestations, or systemic signs.

Alkynes↗
PubMed2002

Analysis of the effect of cannabinoids on GABAergic neurotransmission in the substantia nigra pars reticulata.

The CB(1) cannabinoid receptor is widely distributed in the central nervous system. The substantia nigra pars reticulata (SNR) belongs to the brain regions with the highest density of CB(1) receptors. According to anatomical studies, most of the CB(1) receptors in the SNR are localized on terminals of striatonigral GABAergic neurons. The aim of the present study was to clarify the function of these receptors.Electrophysiological properties of SNR neurons were studied in brain slices with the patch-clamp technique. Inhibitory postsynaptic currents (IPSCs) were elicited in parasagittal slices by electrical stimulation in the internal capsule. The mixed CB(1)/CB(2) cannabinoid receptor agonist WIN55212-2 (1 microM and 10 microM) concentration dependently decreased the amplitude of IPSCs. CP55940, another mixed CB(1)/CB(2) cannabinoid receptor agonist, also lowered IPSC amplitude. Superfused alone, the CB(1)-selective antagonist SR141716A (1 microM) increased the amplitude of IPSCs. In interaction experiments, SR141716A (1 microM) prevented the inhibition produced by WIN55212-2 (1 microM). WIN55212-2 (1 microM) had no effect on GABAergic currents elicited by ejection of muscimol (1 mM) to the surface of the slices. WIN55212-2 (10 microM) did not influence the frequency and amplitude of spontaneously occurring IPSCs (sIPSCs) and the firing rate of SNR neurons. The results show that activation of CB(1) cannabinoid receptors inhibits GABAergic neurotransmission in the SNR. The likely mechanism is presynaptic inhibition of GABA release, since cannabinoids had no effects on currents evoked by direct stimulation of GABA(A) receptors by muscimol and on the amplitude of sIPSCs. The enhancement of IPSCs by the cannabinoid antagonist probably reflects continuous inhibition of GABAergic neurotransmission by an endogenous cannabinoid. SNR neurons receive GABAergic input from three sources: from the corpus striatum, the globus pallidus and from neighbouring SNR neurons. The observed inhibition of GABAergic neurotransmission was probably due to depression of the transmission between striatonigral axons and SNR neurons. No direct actions of cannabinoids on SNR neurons were observed in addition to this synaptic effect.

Animals↗
PubMed2003

The peripheral sympathetic nervous system is the major target of cannabinoids in eliciting cardiovascular depression.

Our objective was to identify the sites of interaction of cannabinoids with cardiovascular sympathetic regulation in the rat. Effects on sympathetic tone were first determined in anaesthetised animals following i.v. administration of the drugs. Central effects were evaluated in anaesthetised rats receiving microinjections of cannabinoids into brain stem nuclei. Peripheral effects were identified in pithed rats with electrically stimulated sympathetic outflow. In anaesthetised and artificially ventilated rats, i.v. injection of the cannabinoid agonists WIN55212-2 and CP55940 decreased mean arterial pressure, heart rate and the plasma noradrenaline concentration. These effects were antagonized by the CB(1) cannabinoid receptor antagonist SR141716A. The bradycardia was abolished by the muscarinic acetylcholine receptor antagonist methylatropine. The decreases in mean arterial pressure and heart rate caused by cannabinoids in ventilated rats were much less pronounced than in spontaneously breathing rats. Microinjection of WIN55212-2 into the nucleus tractus solitarii had no effect. Microinjected into the rostral ventrolateral medulla oblongata, WIN55212-2 lowered mean arterial pressure slightly without changing other parameters. In pithed rats, WIN55212-2 inhibited the increases in mean arterial pressure, heart rate and the plasma noradrenaline concentration evoked by electrical stimulation of the sympathetic outflow. Our results show that activation of CB(1) cannabinoid receptors induces sympathoinhibition and enhancement of cardiac vagal tone, leading to hypotension and bradycardia. Presynaptic inhibition of noradrenaline release from terminals of postganglionic sympathetic neurons is the major component of the sympathoinhibition, but an effect in the rostral ventrolateral medulla oblongata may also contribute. The cannabinoid-evoked cardiovascular depression depends strongly on the respiratory state of the animals.

Animals↗
PubMed2003

Analysis of the respiratory effects of cannabinoids in rats.

The objective of the present study was to evaluate the respiratory effects of cannabinoids and their influence on cardiovascular homeostasis.In spontaneously breathing urethane-anaesthetised rats, intravenous injection of the two synthetic cannabinoid receptor agonists WIN55212-2 and CP55940 strongly and dose-dependently lowered mean arterial pressure, heart rate and the plasma noradrenaline concentration. The cardiovascular depressive effects were associated with a large decrease in respiratory rate, hypoxia, hypercapnia and blood acidosis. All depressor effects of WIN55212-2 were abolished by the selective CB(1) cannabinoid receptor antagonist SR141716A. The bradycardia elicited by WIN55212-2 was inhibited by the muscarinic acetylcholine receptor antagonist methylatropine. The natural agonist Delta(9)-tetrahydrocannabinol also elicited cardiovascular and respiratory depression. In contrast, WIN55212-3, an enantiomer of WIN55212-2 lacking affinity for cannabinoid receptors, had no effect. The cannabinoid-evoked decreases in blood pressure and heart rate were much more pronounced in spontaneously breathing than in artificially ventilated urethane-anaesthetised rats. In contrast, the plasma noradrenaline concentration was lowered equally in both preparations. Our results show that activation of CB(1) cannabinoid receptors not only induces cardiovascular depression, but also markedly impairs ventilation. The second major finding of the present study is that the respiratory depression evoked by cannabinoids largely amplifies the cardiovascular depression.

Anesthesia↗
PubMed2003

Hypotensive effect of anandamide through the activation of CB1 and VR1 spinal receptors in urethane-anesthetized rats.

This study examined the effect of intrathecal (i.t.) injection of the endocannabinoid anandamide in urethane-anesthetized rats. The tip of the i.t. cannula was positioned at the T(12)-L(1) level of the spinal cord. Either anandamide or its metabolically stable analogue methanandamide (25 to 100 nmol) produced dose-dependent decreases in the blood pressure that persisted at least for up to 30 min. The hypotensive responses to 100 nmol anandamide and to 100 nmol methanandamide were -17.7+/-1.6 mmHg ( n=5) and -17.9+/-2.0 mmHg ( n=4), respectively. Hypotensive effects were also obtained with the CB(1) cannabinoid receptor agonist WIN 55212-2 (20 nmol; i.t.) as well as with the vanilloid VR(1) receptor agonist capsaicin (3 nmol; i.t.). Nicotinic ganglionic blockade with hexamethonium bromide [10 mg/kg; intravenous(i.v.)] abolished the responses to both anandamide and capsaicin. The i.t. administration of the CB(1) receptor antagonist, 20 nmol SR 141716A, as well as the VR(1) receptor antagonist, 20 nmol capsazepine, prevented almost completely the hypotensive responses to both anandamide and methanandamide. SR 141716A prevented the hypotension caused by WIN 55212-2 but did not modify the response to the vanilloid receptor agonist capsaicin. On the contrary, capsazepine antagonized the hypotension caused by capsaicin but failed to affect the decrease in blood pressure caused by the CB1 cannabinoid receptor agonist WIN 55212-2. These results suggest that anandamide could modulate the blood pressure through the activation of cannabinoid CB(1) receptors and vanilloid VR(1) receptors localized at the spinal cord.

Anesthesia, Intravenous↗
PubMed2003

CB1- and CB2-cannabinoid receptor-independent lipolysis induced by WIN 55,212-2 in male rat adipocytes.

The expression of genes encoding the cannabinoid CB(1) and CB(2) receptors and fatty acid amide hydrolase (FAAH) and the lipolytic activity of cannabinoid agonists were investigated in rat adipose tissue.RT-PCR studies indicated that the genes encoding CB(1) and CB(2) receptors and FAAH are not expressed in epididymal adipocytes. In functional studies, the non-selective cannabinoid receptor agonist WIN 55,212-2 concentration-dependently (0.01-30 micro M) induced glycerol release above baseline ( E(max) 96.1+/-6.2% of isoprenaline-induced lipolytic response). The selective CB(2) agonist JWH-015 (0.01-30 micro M) had no lipolytic activity while the endocannabinoid 2-arachidonoylglycerol and the stable anandamide derivative, R(+)-methanandamide had, only a weak lipolytic effect at the highest concentrations employed (10 and 30 micro M). The concentration/response relationship for WIN 55,212-2-mediated lipolytic activity, mimicked by the S(-)-enantiomer WIN 55,212-3, was shifted significantly to the right by the CB(1) antagonist AM 251 only at 10 micro M, but was not modified by the beta-adrenoceptor antagonist propranolol (1 micro M). The protein kinase inhibitor H-89, but not the two adenylyl cyclase inhibitors (+/-) N(6)- R-phenylisopropyladenosine (R-PIA, 1 micro M, a selective A(1) adenosine receptor agonist) or SQ 22,536 (50 micro M) significantly reduced the glycerol efflux induced by WIN 55,212-2. Our data suggest that the cannabinoid drug WIN 55,212-2 may exert lipolytic activity in male rat adipocytes via an intracellular mechanism, not activated by CB(1) or CB(2) receptor stimulation, significantly reversed by H-89 but not clearly linked to stimulation of adenylyl cyclase.

Adipocytes↗