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At least 793 records · Page 44Linked to original sources
PubMed2006

The Practical Approach to Lung Health in South Africa (PALSA) intervention: respiratory guideline implementation for nurse trainers.

AIM: This paper describes the design, facilitation and preliminary assessment of a 1-week cascade training programme for nurse trainers in preparation for implementation of the Practical Approach to Lung Health in South Africa (PALSA) intervention, tested within the context of a pragmatic cluster randomized controlled trial in the Free State province. PALSA combines evidence-based syndromic guidelines on the management of respiratory disease in adults with group educational outreach to nurse practitioners. BACKGROUND: Evidence-based strategies to facilitate the implementation of primary care guidelines in low- to middle-income countries are limited. In South Africa, where the burden of respiratory diseases is high and growing, documentation and evaluation of training programmes in chronic conditions for health professionals is limited. METHOD: The PALSA training design aimed for coherence between the content of the guidelines and the facilitation process that underpins adult learning. Content facilitation involved the use of key management principles (key messages) highlighted in nurse-centred guidelines manual and supplemented by illustrated material and reminders. Process facilitation entailed reflective and experiential learning, role-playing and non-judgemental feedback. DISCUSSION AND RESULTS: Preliminary feedback showed an increase in trainers' self-awareness and self-confidence. Process and content facilitators agreed that the integrated training approach was balanced. All participants found that the training was motivational, minimally prescriptive, highly nurse-centred and offered personal growth. CONCLUSION: In addition to tailored guideline recommendations, training programmes should consider individual learning styles and adult learning processes.

Education, Nursing, Continuing↗
PubMed2004

Rapid and efficient incorporation of tissue factor into liposomes.

Tissue factor (TF), the physiological trigger of the blood clotting cascade, is also the active ingredient in thromboplastin preparations which are widely used in clotting assays such as the prothrombin time (PT) test. A type I integral membrane protein, TF must be incorporated into suitable phospholipid membranes for full procoagulant activity. Several methods exist for incorporating TF into phospholipid vesicles, typically employing the formation of mixed micelles containing detergent, phospholipid and TF, followed by detergent removal or dilution below the critical micelle concentration (CMC). These methods have certain drawbacks: they may take several days to complete, employ expensive detergents, are difficult to scale up, and do not always result in complete detergent removal. In this study we have investigated the use of a variety of detergents [Triton X-100, octaethylene glycol monododecyl ether (C(12)E(8)), cholate, deoxycholate, and n-octyl-beta-D-glucopyranoside], and the use of adsorbent beads (Bio-Beads SM-2) for removing detergent, in processes to incorporate TF into proteoliposomes with high specific activity in coagulation assays. The method we have developed is rapid and readily scalable, yielding thromboplastin preparations with specific activities in plasma clotting assays that are at least as high as those made with detergent dialysis.

Blood Coagulation↗
PubMed2004

The influence of formulation and spacer device on the in vitro performance of solution chlorofluorocarbon-free propellant-driven metered dose inhalers.

The purpose of this study was to evaluate the hypothesis that spacer devices have limited effect on the in vitro fine particle dose emitted from solution metered dose inhalers containing different proportions of HFA134a [1,1,1,2,-tetrafluoroethane] propellant. Two solution formulations (80% and 97.5% wt/wt HFA134a) were tested across the actuator alone, actuator plus Aerochamber, and Ace holding chamber. Particle size distributions were determined using laser diffraction (LD) and cascade impaction (CI). Multimodal particle size distributions were identified using LD. CI analyses were characterized by a major mode located at approximately 0.5 microm. The fine particle dose emitted from the inhaler spacer combinations containing 97.5% HFA134a was independent of the device setup used. Fine particle doses were influenced by spacer setup in 80% HFA134a formulations, indicating different plume dynamics of low vapor pressure formulations. Sampling inlet deposition was approximately 0 when spacer devices were used with either formulation. When spacers were not used, sampling inlet deposition was increased significantly. However, inlet deposition with the 97.5% HFA134a formulation was significantly less than that of the 80% HFA134a formulation (approximately 25% of emitted dose compared with 69%, respectively). Thus, high propellant concentration formulations appear to have more robust in vitro performance. This is particularly important given the preponderance of poor patient compliance that is associated with spacer use. High propellant concentrations had the advantage of fine particle doses that were independent of the device setup and significantly lowered sampling inlet deposition when no spacer was used.

Aerosol Propellants↗
PubMed2003

Heat shock and Cd2+ exposure regulate PML and Daxx release from ND10 by independent mechanisms that modify the induction of heat-shock proteins 70 and 25 differently.

Nuclear domains called ND10 or PML bodies might function as nuclear depots by recruiting or releasing certain proteins. Although recruitment of proteins through interferon-induced upregulation and SUMO-1 modification level of PML had been defined, it is not known whether release of proteins is regulated and has physiological consequences. Exposure to sublethal environmental stress revealed a sequential release of ND10-associated proteins. Upon heat shock Daxx and Sp100 were released but PML remained, whereas exposure to subtoxic concentrations of CdCl(2) induced the release of ND10-associated proteins, including PML, with Sp100 remaining in a few sites. In both cases, recovery times were similar and were followed by a burst of mitotic activity. Cadmium-induced release of proteins from ND10 could be blocked by inhibiting activation of p38 MAPK or ERK1/2. By contrast, heat-shock-induced desumolation of PML and release of proteins from ND10 are unaffected by these inhibitors but can be recapitulated by overexpression of the SUMO isopeptidase SENP-1. Therefore, activation of SENP-1-like SUMO isopeptidase(s) during heat shock is not affected by these kinases. Thus, the release of ND10-associated proteins is not due to a general dispersal of nuclear domains but seems to be regulated by rapid desumolation during thermal stress and through the phosphorylation cascade of stress and mitogenic signaling pathways in the case of CdCl(2). Whether the release of certain proteins had consequences was tested for heat-shock-protein transcription and synthesis. Release of Daxx correlated with Hsp25 suppression, suggesting that Daxx normally inhibits immediate Hsp25 production. Release of PML correlated with lower production of Hsp70. These results suggest that segregation or release of PML or Daxx have differential physiological relevance during the stress response. The fact that enzymatic activation of protein release or segregation after stress modifies the heat-shock response strengthens the concept of ND10 as a regulated depot of effector proteins.

Animals↗
PubMed1992

Estrogen suppresses mu-opioid- and GABAB-mediated hyperpolarization of hypothalamic arcuate neurons.

The effects of estrogen on the response of hypothalamic arcuate neurons to mu-opioid and GABAB agonists were investigated. Intracellular recordings were made from arcuate neurons in slices prepared from ovariectomized guinea pigs that were pretreated with estrogen or vehicle. Estrogen shifted the dose-response curve to the mu-opioid agonist DAMGO (Tyr-D-Ala-Gly-MePhe-Gly-ol) by 3.4-fold; the EC50 for DAMGO was 240 +/- 25 nM in estrogen-treated females versus 70 +/- 12 nM in the controls. The maximal hyperpolarization induced by DAMGO was equivalent in neurons from both groups. The Ke for the naloxone antagonism of the DAMGO response was similar in both groups, which would indicate that the affinity of the mu-receptor was unchanged. To explore where in the receptor/G-protein/K+ channel cascade estrogen may be acting to attenuate the mu-opioid-mediated hyperpolarization, the response to the GABAB agonist baclofen was also tested. Estrogen treatment also shifted the dose-response curve for the baclofen-induced hyperpolarization by 3.3-fold without altering the maximum hyperpolarization; the EC50 shifted from 11.0 +/- 4.0 microM to 36.0 +/- 5.0 microM. All of the neurons were identified after linking the intracellular biocytin with streptavidin-FITC, and a subpopulation of cells in both groups were immunoreactive for beta-endorphin. We conclude that estrogen decreases the functional coupling of the mu-opioid and GABAB receptors to the inwardly rectifying K+ channel possibly through an action on the G-protein.

Animals↗
PubMed2004

Testing families with HFE-related hereditary haemochromatosis.

HFE-related hereditary haemochromatosis is the most common autosomal recessive disorder in the Caucasian population. In 1996 the responsible gene (called HFE) was identified. Two mutations (C282Y and H63D) are considered most important and occur frequently in the Caucasian population. We describe a family of an affected proband in which first- and second-degree relatives were tested phenotypically and genotypically. In second-degree relatives both C282Y homozygosity as well as compound heterozygosity were found. Family testing can be useful to detect persons who will possibly develop iron overload. We must be aware that testing first-degree relatives only carries a 2.5% chance that persons at risk of developing iron loading will not be detected. Cascade screening of second-degree relatives might be cost-effective.

Amino Acid Substitution↗
PubMed1982

Prediction of prognosis in intensive care patients.

The treatment of intensive care patients is complex and sometimes unrewarding. The identification of factors that predict the outcome of these patients would make treatment easier to evaluate. Various pulmonary, cardiovascular and metabolic variables have been tested as prognostic measures. They have so far not been found conclusively reliable. It seems as if measurements of factors in the cascade systems, in particular prekallikrein, Hageman factor, and antithrombin III may be the best available indexes to predict a fatal outcome.

Acidosis↗
PubMedDate not supplied

[The physiopathology of acute spinal cord injury and a hope for a successful treatment].

The acute phase of spinal cord injury includes primary and secondary pathological patterns. Primary patterns include the effects of contusion, laceration, stretch of neural tissue and direct vascular trauma. These changes are irreversible. Secondary patterns include posttraumatic ischemic changes, loss of energy metabolism, oedema, release of cytotoxic substances such as free radicals, and electrolyte changes such as an increase in intracellular calcium ions. These changes may be reversible. This determines treatment strategies. Free-radical scavengers, opioid receptor antagonists include TRH and its analogues, calcium channel blockers, volume expander, osmotic diuretics, hypothermia, antioxidants, cycloxygenase inhibitors, serotonin antagonists and NMDA receptor antagonists were tested in experimental models during the last 4 years. The successful treatment should break the feedback loops and trails of secondary injury cascade in many places so combined treatment connected with many elements and surgery decompression is necessary.

Drug Therapy↗
PubMed1998

Fibrin deposition in squamous cell carcinomas of the larynx and hypopharynx.

Extravascular fibrin deposition is frequently observed within and around neoplastic tissue and has been implicated in various aspects of tumor growth. The distribution of fibrin deposits was investigated in squamous cell carcinomas representing different stages of tumor progression of the larynx (n = 25) and hypopharynx (n = 9) by immunofluorescent techniques. Double and treble labelings were used to detect fibrinogen and fibrin in combination with marker antigens for tumor cells (cytokeratin), endothelial cells (von Willebrand factor), macrophages (recognized by KiM7), as well as factor XIII subunit A (FXIIIA) and tenascin (an embryonic extracellular matrix protein newly expressed during tumorigenesis). All tissue samples showed specific staining for fibrinogen/fibrin. Fibrin deposition was localized almost exclusively in the connective tissue compartment of tumors with characteristic accumulation at the interface of connective tissue and the tumorous parenchyma. In certain tumor samples showing highly invasive characteristics, fibrin deposits were observed in close association with tumor blood vessels in the tumor cell nodules. The overlapping reactions with polyclonal antibody to fibrinogen/fibrin and monoclonal antibody to fibrin indicate the activation of the coagulation cascade resulting in in situ thrombin activation and fibrin formation. Fibrin was crosslinked and stabilized by FXIIIA as revealed by urea insolubility test. Accumulation of phagocytozing macrophages detected by Ki M7 monoclonal antibody could be seen in areas of fibrin deposition. The blood coagulation factor XIIIA was detected in and around the cells labeled with Ki M7 antibody. Tenascin and fibrin deposits were found in the same localization in the tumor stroma and in association with tumor blood vessels within the tumor cell nodules. Neither fibrin nor tenascin were detected in the histologically normal tissue adjacent to tumors. The close association between fibrin deposits and macrophage accumulation strongly suggests the active participation of tumor-associated macrophages in the formation of stabilized intratumoral fibrin that facilitates tumor matrix generation and tumor angiogenesis.

Adult↗
PubMed2007

Hierarchical organization via a facilitation cascade in intertidal cordgrass bed communities.

It has recently been proposed that many communities are structured by a hierarchy of interactions in which facilitation by foundation species is of primary importance. We conducted the first explicit experimental test of this hypothesis by investigating the organization of positive interactions on New England cobblestone beaches. In this midintertidal community, wave-generated substrate instability and solar stress largely limit marine organisms to the shelter of cordgrass beds. Cordgrass, which can establish and persist without the aid of other foundation species, facilitates a dense assemblage of inhabitants (e.g., mussels, snails, seaweeds) with roots/rhizomes that stabilize substrate and a dense canopy that baffles waves and provides shade. Within the cordgrass bed community, ribbed mussels further enhance physical conditions and densities of other species (e.g., amphipods, barnacles) by providing crevice space and hard substrate. We conclude that cordgrass bed communities are hierarchically organized: secondary interactions (e.g., facilitation by ribbed mussels) play a key role within an assemblage dependent on primary facilitation by the independently successful foundation species cordgrass. Our results identify emergent indirect positive interactions in the form of facilitation cascades, have broad implications for conservation, and help unify existing models of community organization that were developed without considering the fundamental role of positive interactions.

Animals↗
PubMed1999

The high cost of syncope: cost implications of a new insertable loop recorder in the investigation of recurrent syncope.

BACKGROUND: Patients with recurrent syncope frequently undergo extensive investigations that consume significant health care resources. Recent advances in long-term monitoring techniques have enhanced diagnostic yield in patients with infrequent symptoms. There is little information on the relative cost-effective profile of the investigative tools used in patients with syncope. METHODS: Two methods to determine health care costs in patients with syncope were used. In the first, health care resource utilization was determined in 24 patients with recurrent unexplained syncope and negative investigations who underwent insertion of the implantable loop recorder (ILR) during a pilot study of the feasibility of the device. The costs of investigations before, during, and after ILR implantation in each patient were calculated on the basis of median charges for an index investigation and a regression analysis of 1018 US Medicare hospital claims for syncope from 1993. Charges were converted to costs using a cost-to-charge ratio of 0.64. The second method was based on estimated costs per diagnosis and published diagnostic yields of 6 commonly applied tests in patients with syncope. A cohort simulation using theoretic models of 100 patients undergoing investigation for syncope was created to compare the diagnostic yield and cost per diagnosis of various diagnostic cascades. RESULTS: In the pilot study, the cost of investigation of syncope in the 2 years before ILR insertion was $7584 per patient. After the ILR was inserted, a diagnosis was obtained in 21 of 24 patients (diagnostic yield 88%). The cost of therapy was $2452, followed by a reduction in cost of care to $596 over 30 +/- 10 months of follow-up. In the second method, the diagnostic yield of individual tests ranged from 3% for echocardiography to 88% for the ILR. The cost per diagnosis obtained ranged from $529 for the external loop recorder to $73,260 for electrophysiologic testing in patients without structural heart disease. An approach to syncope similar to that of the ILR pilot study resulted in a cost per diagnosis of $3193 and a diagnostic yield of 98%. Performance of echocardiography in half of the patients and electrophysiologic testing only in the presence of structural heart disease reduced the cost to $2494 and retained a diagnostic yield of 98%. CONCLUSIONS: The cost of investigation of syncope is high. The ILR may reduce health care resource utilization by providing a diagnosis permitting definitive therapy. The cost per diagnosis profile of current diagnostic tests commonly used in patients with syncope is highly variable. A cost-effective approach to diagnosing this disorder can retain a high diagnostic yield with a reduction in resource utilization compared with a conventional approach.

Cost of Illness↗
PubMed2000

Application of combined genetic algorithms with cascade correlation to diagnosis of delayed gastric emptying from electrogastrograms.

The current standard method (radioscintigraphy) for the diagnosis of delayed gastric emptying (GE) of a solid meal involves radiation exposure and considerable expense. Based on combining genetic algorithms with the cascade correlation learning architecture, a neural network approach is proposed for the diagnosis of delayed GE from electrogastrograms (EGGs). EGGs were measured by placing surface electrodes on the abdominal skin over the stomach in 152 patients with suspected gastric motility disorders for 30 min in the fasting state and for 2 h after a standard test meal. The GE rate of the stomach was simultaneously monitored after the meal using radioscintigraphy. Five spectral parameters of EGG data in each patient were used as the inputs to a classifier. The classifier was designed by using genetic algorithms in conjunction with the cascade correlation learning architecture. The main advantage of this technique over the back-propagation (BP) for supervised learning is that it can automatically develop the architecture of neural networks to give a suitable network size for a specific problem. The resulted neural network with three hidden units exhibits 83% correct classification for the EGG data, and has comparable performance with the BP network. This study demonstrates the potential of the neural network approach based on combined genetic algorithms with cascade correlation for diagnosis of gastric emptying from the EGG.

Algorithms↗
PubMed1989

[Pathogenesis and laboratory diagnosis of venous thrombosis].

UNLABELLED: Due to the increasing number of elderly as well as chronically-ill patients, venous thrombosis assumes an increasing role as a typical complication of many courses of disease. Postoperatively, in patients without anticoagulation, fibrinogen tests show venous thrombosis in the lower extremities in up to 50% but not all were clinically relevant. Prophylactic treatment has markedly lowered the manifestation of deep venous thrombosis. Nevertheless, in current epidemiologic studies, the prevalence of thrombotic disease is three-fold higher (1:7,500) than that of bleeding diseases (1:20,000). PATHOGENESIS: Congenital deficiency or congenital dysfunction of inhibitors of activated clotting factors have provided insight into the functional principles of limited proteolysis. Unequivocal causes of recurrent thrombosis are deficiency or dysfunction of AT III, protein C, protein S or plasminogen (Figure 1). Dysfibrinogenemia, in about 10% of the patients, leads to a tendency to thrombosis. Unclarified remains the relevance of lowered values for factor XII, heparin-cofactor II (HC II) and histidine-rich glycoprotein (HRG) (Table 1). Congenital disorders usually manifest themselves in the early adulthood. For the clinical manifestation of venous thrombosis, imbalance between pro-coagulatory and inhibitor factors are of importance, therefore the compensatory capabilities of other protease inhibitors, for example, alpha-2-macroglobulin should be taken into consideration. In acquired lowering of hemostasis factors, the balance in the plasma protein cascade should be assessed (Figure 1).(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Coagulation Tests↗
PubMed1983

Suppressive mechanisms in alloantigen-induced T cell responses.

In this report we examined the possibility that suppression of the mixed lymphocyte response by MLR-TsF results from interference with IL-2 regulation of T cell proliferation. Two distinct processes of inhibition involving both a direct effect on IL-2-driven proliferation of responder T cells, and induction of a second-order suppressor cell (Ts2) were described. Exogenous IL-2 did not abrogate MLR-TsF-induced suppression, and activated responder cells from suppressed cultures expressed functional IL-2 receptors by IL-2 adsorption analysis. Thus, suppression is not due to lack of available IL-2 or to abnormal acquisition of receptors for IL-2 during T cell activation. In contrast, a profound MLR-TsF effect on IL-2-induced proliferation of HT2 cells as well as MLR-activated cells was observed even after presaturation of receptors with excess IL-2. These results differentiated the direct responder cell effect of MLR-TsF from its Ts2 inductive capacity, and localized the defect in responder cell proliferation to events occurring subsequent to IL-2 binding. When analyzed in terms of proposed models for hormone-receptor interactions, characteristic dose-response curves similarly predict a postreceptor defect. Examination of the Ts2 pathway of suppression revealed a late-acting inhibitory effect peaking 72 h after MLR initiation. A minor part of Ts2 activity was susceptible to exogenous IL-2, and may reflect a requirement for IL-2 during Ts2 expansion. However, the most significant component of Ts2-mediated suppression was resistant to excess IL-2, and IL-2 production was normal in Ts2-regulated cultures, thus ruling out limitation of IL-2 for responder cell use as the major mechanism of Ts2 suppression. The complete pathway of Ts2 suppression and its functional relationship to other MLR-TsF inhibitory activities is not yet fully understood. However, these results suggest that the ultimate mechanisms of alloantigen-induced suppression involve late events of the IL-2-dependent lymphokine cascade.

Animals↗
PubMed2003

Persistent changes in spontaneous firing of Purkinje neurons triggered by the nitric oxide signaling cascade.

Many types of neurons fire spontaneously because of the activity of pacemaking ion channels. Although endogenous firing can serve as a persistent signal to downstream targets, little attention has been paid to factors that might modulate such intrinsic electrical activity. We tested for modulation of spontaneous firing of Purkinje neurons in cerebellar slices under conditions in which principal synaptic inputs were blocked. Loose-patch recordings from single neurons show that sustained (>40 min) increases in the spontaneous firing rate can be triggered by activation of the nitric oxide-cGMP signaling pathway. Inhibitors of soluble guanylate cyclase and protein kinase G block this modulation. Increases in firing rate are also observed after stimulation of parallel fibers but not in response to basket cell activity. These findings elucidate a novel role for the nitric oxide-cGMP signaling cascade in the brain. This mechanism could permit long-term adjustments in the baseline firing rate of endogenously active neurons in response to changes in afferent activity.

Action Potentials↗
PubMed2005

Comparison of cascade impaction and laser diffraction for particle size distribution measurements.

The Andersen cascade impactor (ACI) and laser diffraction (LD) can be correlated at ambient temperature for aqueous drug formulations atomized by Soft Mist inhalers. A comparison of the two particle size determination methods at different conditions (flow rate, relative humidity) was performed. Under well-defined conditions, the faster LD can substitute the time consuming ACI at least for routine tests. The measurements were performed with three different drug formulations. The aerosol was generated by Soft Mist inhalers, and the droplet distributions were measured simultaneously using a laser diffraction analyzer together with the eight-stage Andersen cascade impactor. The simultaneous measurements ensure that aerosol and air conditions are identical for both LD and ACI. In order to measure the scattered laser light intensity of the aerosol passing the induction port, glass windows were fitted to the induction port. The evaporation effect of the aqueous aerosols on the PSD was investigated at ambient humidity and high humidity (RH > 90%). The simultaneous determination of the droplet size distribution leads to a good correlation between the ACI and LD method only if the measurements were performed at RH of >90%. The humidity of the ambient air had the strongest influence on PSD not only for ACI, but also for LD. In our set-up, the almost saturated air prevents aqueous droplets from drying. The influence of the flow rate on LD was negligible, whereas for ACI, a flow rate dependence is expected. The advantages of LD and the demonstrated compatibility to established EP/USP methods motivate the substitution of the ACI and the use of LD for routine measurements.

Aerosols↗
PubMed2006

H pylori stimulates proliferation of gastric cancer cells through activating mitogen-activated protein kinase cascade.

AIM: To explore the mechanism by which H pylori causes activation of gastric epithelial cells. METHODS: A VacA (+) and CagA (+) standard H pylori line NCTC 11637 and a human gastric adenocarcinoma derived gastric epithelial cell line BGC-823 were applied in the study. MTT assay and (3)H-TdR incorporation test were used to detect the proliferation of BGC-823 cells and Western blotting was used to detect the activity and existence of related proteins. RESULTS: Incubation with H pylori extract increased the proliferation of gastric epithelial cells, reflected by both live cell number and DNA synthesis rate. The activity of extracellular signal-regulated protein kinase (ERK) signal transduction cascade increased within 20 min after incubation with H pylori extract and appeared to be a sustained event. MAPK/ERK kinase (MEK) inhibitor PD98059 abolished the action of H pylori extract on both ERK activity and cell proliferation. Incubation with H pylori extract increased c-Fos expression and SRE-dependent gene expression. H pylori extract caused phosphorylation of several proteins including a protein with molecular size of 97.4 kDa and tyrosine kinase inhibitor genistein inhibited the activation of ERK and the proliferation of cells caused by H pylori extract. CONCLUSION: Biologically active elements in H pylori extract cause proliferation of gastric epithelial cells through activating tyrosine kinase and ERK signal transduction cascade.

Adenocarcinoma↗
PubMed2002

Impaired D2 dopamine receptor function in mice lacking type 5 adenylyl cyclase.

Dopamine receptor subtypes D1 and D2, and many other seven-transmembrane receptors including adenosine receptor A2A, are colocalized in striatum of brain. These receptors stimulate or inhibit adenylyl cyclases (ACs) to produce distinct physiological and pharmacological responses and interact with each other synergistically or antagonistically at various levels. The identity of the AC isoform that is coupled to each of these receptors, however, remains unknown. To investigate the in vivo role of the type 5 adenylyl cyclase (AC5), which is preferentially expressed in striatum, mice deficient for the AC5 gene were generated. The genetic ablation of the AC5 gene eliminated >80% of forskolin-induced AC activity and 85-90% of AC activity stimulated by either D1 or A2A receptor agonists in striatum. However, D1- or A2A-specific pharmaco-behaviors were basically preserved, whereas the signal cascade from D2 to AC was completely abolished in AC5(-/-), and motor activity of AC5(-/-) was not suppressed by treatment of cataleptic doses of the antipsychotic drugs haloperidol and sulpiride. Interestingly, both haloperidol and clozapine at low doses remarkably increased the locomotion of AC5(-/-) in the open field test that was produced in part by a common mechanism that involved the increased activation of D1 dopamine receptors. Together, these results suggest that AC5 is the principal AC integrating signals from multiple receptors including D1, D2, and A2A in striatum and the cascade involving AC5 among diverse D2 signaling pathways is essential for neuroleptic effects of antipsychotic drugs.

Adenylyl Cyclases↗