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At least 253 records · Page 14Linked to original sources
PubMed1989

Dopamine uptake by the human platelet: effects of dopamine receptor agonists.

The uptake of dopamine by human platelets has been shown to be temperature- and energy-dependent and not to occur as a result of dopamine binding to and then being internalised with the dopamine D-1 or D-2 receptor. However, occupancy of these receptors could affect dopamine uptake by platelets through their second messenger systems. We have therefore studied the effect of dopamine receptor agonists, which stimulate receptor second messenger systems, on dopamine uptake by platelets. Uptake of [3H]dopamine by human platelets was not affected by the dopamine D-1 receptor agonist SKF 38393 or the dopamine D-2 receptor agonists, quinpirole and bromocriptine. In contrast, the uptake of [3H]dopamine was decreased by the mixed dopamine receptor agonists dopamine and 2-amino-6,7-dihydroxy-1,2,3,4-tetrahydronaphthalene (ADTN). Furthermore, [3H]ADTN, like [3H]dopamine, was taken up by platelets. In conclusion ADTN, a compound structurally similar to dopamine appears to complete for the dopamine uptake system on the human platelet. Thus, our data further support the hypothesis that a selective dopamine uptake system is present on the human platelet and that this system is not influenced by the dopamine D-1 or D-2 receptor.

Blood Platelets↗
PubMed1997

Modulation of the expression of early genes by polyunsaturated fatty acids.

Expression of early genes is a characteristic immediate cellular response to mitogenic or inflammatory stimulation. Various second messenger systems have been found to transduce the signal from the plasma membrane to the nucleus. Recent observations indicate that in addition to well characterized second messenger systems, polyunsaturated fatty acids, especially the n-6 fatty acid arachidonic acid and its endogenously produced metabolites affect the expression of early genes in different cell types. At least in fibroblasts, the stimulatory effect of arachidonic acid can be antagonized by n-3 polyunsaturated fatty acids. Further identification of the mechanisms through which polyunsaturated fatty acids modulate early gene expression and regulate subsequent cellular responses, like cell growth, may help to define novel concepts in the management of cardiovascular diseases.

3T3 Cells↗
PubMedDate not supplied

Prostaglandin E receptors in myometrial cells.

Prostaglandins (PGs) exert their effects via binding to specific cell surface receptors and influencing second messenger systems through G-proteins. PGE2 may interact with at least four receptor subtypes (EP1, EP2, EP3, EP4), each showing different pharmacological profiles. The second messengers calcium, inositol phosphates (InsPs) and cyclic nucleotides play decisive roles in uterine contractility. The question in this investigation was, which EP receptors, G-proteins and second messenger systems transmit PGE2 induced signals in human myometrium. We have measured changes in InsPs and cAMP formation and also in intracellular calcium concentration ([Ca2+]i) induced by PGE2 and receptor subtype selective analogues in cultured human myometrial cells. PGE2 increased cAMP level and this effect was shared by the EP2 receptor subtype selective agonist Butaprost and by Misoprostol (EP3 > EP2 > EP1). Sulprostone (EP3 > EP1) did not stimulate adenylyl cyclase activity per se, but inhibited forskolin-stimulated adenylyl cyclase in a pertussis toxin (PT) sensitive way. PGE2, GR63799X (EP3 selective), Sulprostone and Misoprostol activated phospholipase-C (PLC), this effect was resistant to PT treatment. PGE2 also elevated [Ca2+]i from the resting level of 60-90 nM up to 350 nM. Low concentrations (1-300 nM) of PGE2 increased [Ca2+]i without PLC activation. The selective EP1 inhibitor AH6809, Nifedipine, Verapamil and PT treatment inhibited this effect of PGE2. In cultured human myometrial cells PGE2 interacts with EP1 receptors, which elevate [Ca2+]i independently from PLC, but involving a Gi protein and plasmamembrane calcium channels; EP2 receptors which stimulate adenylyl cyclase; EP3A receptors, which inhibit adenylyl cyclase activity through Gi activation and EP3D receptors which activate PLC through a PT-insensitive pathway and also elevate [Ca2+]i.

Calcium↗
PubMed1996

Effects of prostaglandins on deoxyribonucleic acid and aggrecan synthesis in the RCJ 3.1C5.18 chondrocyte cell line: role of second messengers.

PGs play an important role in regulating articular chondrocyte function in both normal and pathological states. However, the mechanisms of the effects of PG on chondrocyte function remain undefined. We, therefore, examined the effects of PGE1, PGE2, and PGE2 alpha on second messenger generation in relation to DNA and aggrecan synthesis in the nontransformed rat RCJ 3.1C5.18 (RCJ) chondrocyte cell line. RCJ cells were grown under minimal attachment conditions on a composite collagen-agarose (0.15%/0.8%) gel to maintain a differentiated phenotype. PGE1 and PGE2 (0.001-100 microM) produced a similar dose-related increase in cAMP accumulation, with a maximal 8-fold increase over basal values, whereas PGF2 alpha produced a minimal 1.3-fold increase in cAMP levels only at 100 microM. On the other hand, both PGE2 and PGE2 alpha raised the intracellular free calcium ([Ca2+]i) concentration, derived primarily from extracellular sources, whereas PGE1 was without effect on [Ca2+]i. These three PGs also had divergent effects on DNA synthesis, as measured by [3H]thymidine ([3H]TdR) incorporation. PGF2 alpha (0.001-5 microM) produced a dose-related increase in [3H]TdR incorporation, with a maximal 1.6-fold increase over baseline values at 5 microM and a slight decline to below maximal levels at 10 microM. PGE2 exhibited a contrasting inverse biphasic response, with an initial small suppressive effect that was maximal at 0.1 microM and a secondary stimulatory phase producing a small increase over control values at 5 microM. PGE1 had a uniformly suppressive effect, producing a 30% decrease at 10 microM. Despite the divergent effects of PGE1, PGE2, and PGE2 alpha on second messenger generation and DNA synthesis, all three PGs produced a dose-related stimulation of aggrecan synthesis. PGF2 alpha was the most potent, producing significant stimulation at 0.001 microM and a maximal 104% increase at 5 microM. PGE1 and PGE2 were approximately equipotent and approximately 60% as effective as PGF2 alpha in stimulating aggrecan synthesis. Northern analysis demonstrated that the effects of PG on aggrecan synthesis were not accompanied by changes in aggrecan core protein steady state messenger RNA levels. Thus, the effects of PG on aggrecan production in RCJ cells appear to be regulated at the posttranscriptional level. Forskolin and (Bu)2cAMP mimicked the suppressive effects of PGE1 on [3H]TdR incorporation, as well as the stimulatory effect of PGE1 on aggrecan synthesis. In addition, the phorbol ester 12-O-tetradecanoyl phorbol acetate mimicked PGF2 alpha stimulation of [3H]TdR incorporation and aggrecan synthesis, and the effects of PGE2 alpha on these processes were blocked by protein kinase C inhibitors. Therefore, it appears that in mammalian chondrocytes, PGE1 primarily activates the cAMP-protein kinase A second messenger system, PGE2 alpha affects primarily the Ca2(+)-protein kinase C system, and PGE2 activates both pathways. Moreover, PG posttranscriptional regulation of aggrecan synthesis in chondrocytes involves both the cAMP-protein kinase A and Ca2(+)-protein kinase C second messenger systems.

Aggrecans↗
PubMed2002

The C domain of netrin UNC-6 silences calcium/calmodulin-dependent protein kinase- and diacylglycerol-dependent axon branching in Caenorhabditis elegans.

Second messenger systems mediate neuronal responses to extracellular factors that elicit axon branching, turning, and guidance. We found that mutations in Caenorhabditis elegans that affect components of second messenger systems, a G-protein subunit, phospholipase Cbeta, diacylglycerol (DAG) kinase, and calcium/calmodulin-dependent protein kinase (CaMKII), have no obvious effect on axon responses to UNC-6 except in animals in which the N-terminal fragment, UNC-6DeltaC, is expressed. In these animals, the mutations enhance or suppress ectopic branching of certain axons. Netrin UNC-6 is an extracellular protein that guides circumferential migrations, and UNC-6DeltaC has UNC-6 guidance activity. We propose that the guidance response elicited by the UNC-6 N-terminal domains involves mechanisms that can induce branching that is sensitive to CaMKII- and DAG-dependent signaling, and that the UNC-6 C domain is required in cis to the N-terminal domains to silence the branching and to maintain proper axon morphology.

Alleles↗
PubMed1989

Noradrenaline induces the polyploidization of smooth muscle cells: the synergism of second messengers.

The effect of noradrenaline (NA) on DNA replication of cultured smooth muscle cells (SMC) isolated from rat aorta was examined. It was found that 10 microM NA significantly increased (approximately by twofold) the frequency of tetraploid cells. Cultivation of 4C cells isolated by flow cytometric cell sorting revealed that they were true polyploid cells. This receptor-mediated effect of NA was blocked only by simultaneous action of alpha- and beta-adrenoreceptor antagonists. SMC polyploidization was also stimulated by simultaneous application of direct activators of "second messenger" systems forskolin and phorbolmyristate-acetate. Thus, NA may be one of mediators of the "hypertensive" response of vessel wall SMC, which probably occurs due to synergism of two second messenger systems.

Animals↗
PubMed1989

Mammalian phosphoinositide-specific phospholipase C isoenzymes.

Procaryotic and eucaryotic cells have evolved multiple pathways for communication with their external environment. The inositol 1,4,5-trisphosphate/diacylglycerol second messenger system is an example of such a signal transduction pathway which is present in multicellular eucaryotic organisms. Binding of an agonist to a specific cell surface receptor promotes rapid hydrolysis of phosphatidylinositol 4,5-bisphosphate. The pivotal enzyme for this second messenger system is phosphoinositide-specific phospholipase C which hydrolyzes phosphatidylinositol 4,5-bisphosphate to generate the two second messengers, inositol 1,4,5-trisphosphate and diacylglycerol. Recently, much progress has been made in the purification, characterization and cDNA cloning of multiple PI-PLC isoenzymes. The results of the recent studies on phosphoinositide-specific phospholipase C are reviewed.

Amino Acid Sequence↗
PubMed1998

Repeated exposure of adult rats to Aroclor 1254 causes brain region-specific changes in intracellular Ca2+ buffering and protein kinase C activity in the absence of changes in tyrosine hydroxylase.

Polychlorinated biphenyls (PCBs) are ubiquitous environmental contaminants, some of which may be neurotoxic. In vitro studies from this laboratory indicated that noncoplanar PCBs perturbed intracellular signal transduction mechanisms including Ca2+ homeostasis, receptor-mediated inositol phosphate production, and translocation of protein kinase C (PKC). In the present study, we examined the effects of PCBs in vivo by dosing adult male Long-Evans rats orally with Aroclor 1254 (0, 10, or 30 mg/kg/day; 5 days/week for 4 weeks) in corn oil. At 24 h after the last dose, rats were tested for motor activity in a photocell device for 30 min. Immediately, the rats were euthanized, blood was collected for thyroid hormone analysis, and brains were removed, dissected into regions (cerebellum, frontal cortex, and striatum), and subcellular fractions were obtained for neurochemical analysis. Following Aroclor 1254 treatment, body weight gain in the high-dose group was significantly lower than the control and low-dose groups. Horizontal motor activity was significantly lower in rats dosed with 30 mg/kg Aroclor 1254. Ca2+ buffering by microsomes was significantly lower in all three brain regions from the 30 mg/kg group. In the same dose group, mitochondrial Ca2+ buffering was affected in cerebellum but not in cortex or striatum. Similarly, total cerebellar PKC activity was decreased significantly while membrane-bound PKC activity was significantly elevated at 10 and 30 mg/kg. PKC activity was not altered either in cortex or the striatum. Neurotransmitter levels in striatum or cortex were slightly altered in PCB-exposed rats compared to controls. Furthermore, repeated oral administration of Aroclor 1254 to rats did not significantly alter forebrain tyrosine hydroxylase immunoreactivity or enzymatic activity. Circulating T4 (total and free) concentrations were severely depressed at both doses in Aroclor 1254-exposed rats compared to control rats, suggesting a severe hypothyroid state. These results indicate that (1) in vivo exposure to a PCB mixture can produce changes in second messenger systems that are similar to those observed after in vitro exposure of neuronal cell cultures; (2) second messenger systems seem to be more sensitive than alterations in neurotransmitter levels or tyrosine hydroxylase involved in dopamine synthesis during repeated exposure to PCBs; and (3) the observed motor activity changes were independent of changes in striatal dopamine levels.

Animals↗
PubMed1994

[Atypical binding sites of low density lipoproteins in human vascular smooth muscle cells].

Lipoprotein-binding sites on cultured human omental vascular smooth muscle cells have been investigated. Two sites specifically binding low density lipoprotein (Kd1 = 1 microgram/ml and Kd2 = 50 micrograms/ml) were found. The properties of the high affinity site are similar to those of the previously described "classical" apo B,E-receptor. The nature of the second site is not clear. Binding to this low affinity site is saturable at physiological concentrations of LDL, is reversible and demonstrates a significant selectivity for LDL as compared to HDL3. In contrast with the apo B,E-receptor, the interaction of LDL with the low affinity site is not heparin-sensitive, does not require the presence of bivalent cations and is not abolished after modification of lysine residues of apo B. The kinetic characteristics of the LDL interaction with the low affinity site are in good correlation with the parameters of activation of second messenger systems. The Kd2 value of LDL binding is close to the LDL concentration inducing a half-maximal elevation of inositol phosphates and cytoplasmic Ca2+ level. Acetylation or carbamylation of apo B does not influence the ability of LDL to activate cell-signalling systems. Also, LDL-induced activation of the phosphoinositide turnover is not sensitive to heparin and EDTA. The data obtained support the hypothesis that the low affinity LDL-binding site mediates lipoprotein-induced activation of second messenger systems in human vascular smooth muscle cells.

Acetylation↗
PubMed2000

Modes of control of insect Malpighian tubules: synergism, antagonism, cooperation and autonomous regulation.

Rates of fluid and ion secretion by insect Malpighian tubules are controlled by peptides, including CRF-related peptides and kinins, and in some species by serotonin. It now appears to be a general rule that tubule secretion rate is controlled through the interaction of two or more haemolymph-borne factors. In this review we suggest that these interactions may be classified as synergistic, cooperative, or antagonistic. When presented together, two diuretic factors may act in synergism, so that fluid secretion is stimulated to a greater extent than the sum of their individual effects. Synergism may involve one or more second messenger systems. Alternatively, diuretic factors may act in cooperation, so that although their overall effects are additive, cation and anion transport pathways are controlled separately by distinct second messenger systems. There is also one example of antagonism between factors controlling tubule secretion and between their respective second messengers; one factor is stimulatory, the other is inhibitory. In addition to the complex control of fluid and ion transport by haemolymph-borne factors, sophisticated autonomous regulatory mechanisms have been identified in Malpighian tubules. When triggered by appropriate stimuli, these mechanisms play homeostatic roles, preserving haemolymph osmolality or ionic composition.

Journal Article↗
PubMed1994

Effects of odorants on pigment aggregation and cAMP in fish melanophores.

Odor perception within olfactory neuroepithelium and pigment translocation within melanophores both seem to rely on a cAMP-based second messenger system. From studies on cultured frog melanophores, Lerner et al. (Proc. Natl. Acad. Sci. USA 85:261-264, 1988) suggested that some aspect of odor perception may be mediated by a nonspecific mechanism whose signal is transduced by a cAMP-based second messenger system. In the present study, odorants (beta-ionone, benzylaldehyde, cineole, cinnamaldehyde, and octanol), which previously have been shown to stimulate formation of cAMP in the olfactory neuroepithelium, were investigated for possible pigment dispersing and cAMP-increasing effects. Pretreatment of fish melanophores with the adenylate cyclase activator forskolin (1 microM) resulted in an approximately 300% increase in cAMP and an almost complete blockage of noradrenaline-induced pigment aggregation. However, none of the tested odorants were able to increase the cAMP level and only cinnaldehyde and beta-ionone were found to have any pigment dispersing activity.

1-Octanol↗
PubMed1988

Calcium in the regulation of gravitropism by light.

The red light requirement for positive gravitropism in roots of corn (Zea mays cv "Merit") provides an entry for examining the participation of calcium in gravitropism. Applications of calcium chelators inhibit the light response. Calcium channel blockers (verapamil, lanthanum) can also inhibit the light response, and a calcium ionophore, A23187, can substitute for light. One can substitute for red light by treatments which have elsewhere been shown to trigger Ca2+ influx into the cytosol, e.g. heat or cold shock. Agents which are known to be agonists of the phosphatidylinositol second messenger system (serotonin, 2,4-dichlorophenoxyacetic acid, deoxycholate) can each partially substitute for the red light, and Li+ can inhibit the light effect. These experiments suggest that the induction of positive gravitropism by red light involves a rise in cytoplasmic Ca2+ concentration, and that a contribution to this end may be made by the phosphatidylinositol second messenger system.

Calcimycin↗
PubMed1994

Second messenger signalling during hormone-induced Xenopus oocyte maturation.

Although much information about such processes as cell cycle control, second messenger systems, protein kinases and steroid hormone action has been collected from studies of Xenopus oocyte maturation, we still have very little idea about how the steroid hormone, progesterone, signals the resumption of meiosis from the oocyte plasma membrane. In this review we re-examine the data on second messenger systems in Xenopus oocytes and discuss some of the unresolved questions about hormone signal transduction during maturation. We outline some reasons for the contradictions in the literature and offer some suggestions for avenues of future research.

Animals↗
PubMed1992

Identification of distinct populations of PI-3 kinase activity following T-cell activation.

Activation of mature CD4+ T lymphocytes by antigen-presenting cells involves engagement of the CD3/T-cell antigen receptor complex along with the CD4 surface glycoprotein and the phosphorylation of cellular proteins on tyrosine residues leading to stimulation of a variety of cellular second-messenger systems. Several recent studies have implicated non-receptor protein tyrosine kinase of the src family, especially p56lck and p59fyn, in mediating at least a portion of these tyrosine phosphorylation events. In the present study we have examined the involvement of one type of second-messenger system, phosphatidylinositol-3 kinase (PI-3 kinase), in signal transduction during antibody-induced activation of normal resting human CD4+ T cells. We demonstrate that PI-3 kinase activity is increased following co-approximation of CD4 with the T-cell receptor and that PI-3 kinase activity co-precipitates with the CD4-p56lck complex. We also show that following T-cell activation a complex containing PI-3 kinase activity can be demonstrated in CD3 epsilon immunoprecipitates which is distinct from that which interacts with p56lck.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1992

Structural subtypes of the dopamine D2 receptor are functionally distinct: expression of the cloned D2A and D2B subtypes in a heterologous cell line.

Dopamine, a major neurotransmitter in the mammalian nervous system, exerts its physiological effects through receptors of the G-protein-coupled receptor superfamily. Two major classes of dopamine receptor, D1 and D2, are distinguishable by both biochemical and pharmacological criteria. D1 receptors activate adenylyl cyclase, whereas the D2 class of receptors inhibits this second messenger system. Two subtypes of the human dopamine D2 receptor are generated by alternate splicing of the RNA transcript of a single gene. These two forms, termed D2A (long) and D2B (short), differ by the insertion of 29 amino acids within the putative third cytoplasmic loop, an intracellular domain thought to have a role in coupling this class of receptors to particular second messenger systems. We report here that the D2A and D2B structural subtypes are also functionally distinct. Expression of the two subtypes in a fibroblast cell line revealed that while occupation of both receptors leads to an increase in cytosolic free calcium concentration, they differ in their capacity to inhibit cAMP production. At physiological dopamine concentrations, the D2B-mediated inhibition of calcitonin gene-related peptide-stimulated cAMP accumulation is almost double the response mediated by the D2A subtype. Furthermore, the D2B subtype can maximally attenuate cAMP accumulation by up to 85%, whereas the D2A subtype is less effective, maximally inhibiting cAMP accumulation by only 64%. The D2A and D2B subtypes, thus, constitute functionally distinct forms of the dopamine receptor that can couple to multiple intracellular signalling pathways.

Animals↗
PubMed1992

Interleukin-1 and beta-cell function: more than one second messenger?

Cytokines, in particular IL-1, released mainly by infiltrating macrophages, can be one of the key mediators of immune-induced beta-cell destruction in IDDM. IL-1 is able to induce suppression of insulin release and biosynthesis in cultured rat pancreatic islets. In addition, the cytokine shows clear cytotoxic effects leading to beta-cell death. The proposed mechanisms of action of IL-1 after binding to the beta-cell receptors are varied. Concerning the cytotoxic effects of the cytokine, the role of oxygen free radicals, mainly derived from arachidonate metabolism (see Fig. 1) is clear, and possibly potentiated by a cytosolic Na(+)-mediated alkalinization of the beta-cell exposed to the cytokine. In fact, an increased influx of Na+ may explain some of the cytotoxicity since it results in concomitant water uptake leading to swelling of the endoplasmic reticulum. NO formation also seems to be related to the cytokine-induced cytotoxicity since inhibition of the NO synthase abolishes the effects of the cytokine (see Fig. 1). In relation to the inhibitory effects of the cytokine on the beta-cell, different studies point toward almost all known second messenger systems already described for several hormones, such as cAMP formation, increased phospholipase C activity, changes in cytosolic Ca++, and altered gene transcription (see Fig. 1). Of particular interest is the protease activation associated with IL-1 (a serine protease) that seems to be clearly connected with the effects of the cytokine upon the beta-cell. In conclusion, the different studies devoted to the problem of IL-1 signal transduction on the beta-cell seem to indicate that the action of the cytokine on the pancreatic insulin-secreting cells is not associated with an individual second messenger system but rather seems to be related to a plurifactorial transduction system.

Animals↗
PubMed1995

Increased nitric oxide synthase activities and L-[3H]arginine uptake in brain following portacaval anastomosis.

Glutamatergic synaptic dysfunction has been proposed as a causal factor in portal-systemic encephalopathy. Increased in vitro and in vivo glutamate release and decreased glutamate binding to NMDA receptors were previously reported in the brains of portacaval-shunted rats. Such changes could lead to alterations in the second messenger systems coupled to glutamate receptors. As NMDA receptors have been shown to act via the nitric oxide/cyclic GMP second messenger system, we studied the activities of constitutive nitric oxide synthase (NOS) in the brains of rats following portacaval shunting. Results demonstrate that NOS activities are significantly increased in cerebellum (by 54%, p < 0.01), cerebral cortex (by 65%, p < 0.01), hippocampus (by 88%, p < 0.01), and striatum (by 64%, p < 0.01) of shunted rats compared with sham-operated controls. As L-arginine transport is a prerequisite for nitric oxide production, we also studied L-[3H]arginine transport into cerebellar and cerebral cortical synaptosomes prepared from the brains of portacaval-shunted and sham-operated rats. L-[3H]Arginine uptake was significantly increased (by approximately 50%, p < 0.01) in both cerebellum and cortex. Increased NOS activities of neuronal and/or astrocytic origin and the resultant increased production of nitric oxide in brain could be the consequence of increased NMDA receptor activation following portacaval shunting. Furthermore, increased nitric oxide production could contribute to the increased cerebral blood flow consistently observed following portacaval shunting.

Amino Acid Oxidoreductases↗
PubMed1993

Suppression of lymphocyte adenosine 3':5'-cyclic monophosphate (cAMP) by delta-9-tetrahydrocannabinol.

Delta-9-tetrahydrocannabinol (THC) is the major psychoactive component of marijuana. Suppression of mitogen-stimulated blastogenesis of human lymphocytes in vitro by THC was previously demonstrated. This effect was shown to be concentration dependent with the non-toxic concentrations 5, 7.5, and 10 micrograms THC/ml showing the greatest suppression. However, the mechanism(s) by which THC induces suppression are still unclear. The current study examines the effect of THC on the adenosine 3':5'-cyclic monophosphate (cAMP) pathway second messenger system, which is involved in activation of human peripheral blood lymphocytes. Lymphocyte cAMP levels were stimulated using three hormone receptor stimulators, isoproterenol, histamine, or 5'-N-ethylcarboxamide adenosine (NECA), each of which utilizes a different receptor to enhance cAMP production. THC suppressed cAMP levels independently of the hormone and receptor utilized. Levels of cAMP in non-mitogen-stimulated peripheral blood mononuclear cells and plastic non-adherent lymphocytes, as well as cells stimulated with phytohemmagglutinin, were suppressed by THC. Suppression of cAMP production by THC was further examined to determine whether inhibition involved a GTP-binding protein (Gi), which is known to down-regulate cAMP production. Cells were pre-treated with pertussis toxin to inhibit Gi activity; this blocked the THC-induced suppression of cAMP production. These results suggest that THC can exert its effects on second messenger systems at the lymphocyte membrane level, and that a pertussis toxin-sensitive Gi protein may be involved. Thus, second messenger regulated pathways may be involved in THC-induced immune suppression. However, the relationship between alteration of cAMP production and suppression of lymphocyte function due to the presence of THC in the medium remains to be established.

Adult↗