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Adaptation is increasingly recognised as essential when dealing with the adverse impacts of climate change on societies, economies and the environment. However, there is insufficient information about the effectiveness of adaption policies, measures and actions. For this reason, the establishment of monitoring programmes is considered to be necessary. Such programmes can contribute to knowledge, learning and data to support adaptation governance. In the European Union (EU), member states are encouraged to develop National Adaptation Strategies (NASs). The NASs developed so far vary widely because of differing views, approaches and policies. A number of member states have progressed to monitoring and evaluating the implementation of their NAS. It is possible to identify key elements in these monitoring programmes that can inform the wider policy learning process. In this paper, four generic building blocks for creating a monitoring and evaluation programme are proposed: (1) definition of the system of interest, (2) selection of a set of indicators, (3) identification of the organisations responsible for monitoring and (4) definition of monitoring and evaluation procedures. The monitoring programmes for NAS in three member states-Finland, the UK and Germany-were analysed to show how these elements have been used in practice, taking into account their specific contexts. It is asserted that the provision of a common framework incorporating these elements will help other member states and organisations within them in setting up and improving their adaptation monitoring programmes.

Background: Current air quality standards for particulate matter (PM) use the PM mass concentration [PM with aerodynamic diameters ≤ 10 μm (PM(10)) or ≤ 2.5 μm (PM(2.5))] as a metric. It has been suggested that particles from combustion sources are more relevant to human health than are particles from other sources, but the impact of policies directed at reducing PM from combustion processes is usually relatively small when effects are estimated for a reduction in the total mass concentration., Objectives: We evaluated the value of black carbon particles (BCP) as an additional indicator in air quality management., Methods: We performed a systematic review and meta-analysis of health effects of BCP compared with PM mass based on data from time-series studies and cohort studies that measured both exposures. We compared the potential health benefits of a hypothetical traffic abatement measure, using near-roadway concentration increments of BCP and PM(2.5) based on data from prior studies., Results: Estimated health effects of a 1-μg/m3 increase in exposure were greater for BCP than for PM(10) or PM(2.5), but estimated effects of an interquartile range increase were similar. Two-pollutant models in time-series studies suggested that the effect of BCP was more robust than the effect of PM mass. The estimated increase in life expectancy associated with a hypothetical traffic abatement measure was four to nine times higher when expressed in BCP compared with an equivalent change in PM(2.5) mass., Conclusion: BCP is a valuable additional air quality indicator to evaluate the health risks of air quality dominated by primary combustion particles.

This statement is the result of discussions held at the 2005 NERAM IV Colloquium "International Perspectives on Air Quality: Risk Management Principles for Policy Development" and represents the collective views of 35 delegates, including international air quality policy analysts, academics, nongovernmental organizations, industry representatives, and decision makers from Mexico, Canada, the United States, the United Kingdom, Brazil, Hong Kong, and The Netherlands on principles for global air quality management. The objective of the colloquium was to "establish principles for air quality management based on the identification of international best practice in air quality policy development and implementation." This statement represents the main findings of a breakout group discussion session, presentations of an international panel of speakers from Canada, the United States, Mexico, and Hong Kong and views of the delegates expressed in plenary discussions. NERAM undertook a transparent process to try to ensure that the statement would accurately reflect the conference discussions, including documenting the proceedings and inviting delegates' comments on draft versions of the statement.

Residence in urban areas with much traffic has been associated with various negative health effects. However, the contribution of traffic emissions to these adverse health effects has not been fully determined. Therefore, the objective of this in vivo study is to compare the pulmonary and systemic responses of rats exposed to particulate matter (PM) obtained from various locations with contrasting traffic profiles. Samples of coarse (2.5 microm-10 microm) and fine (0.1 microm-2.5 microm) PM were simultaneously collected at nine sites across Europe with a high-volume cascade impactor. Six PM samples from various locations were selected on the basis of contrast in in vitro analysis, chemical composition, and traffic profiles. We exposed spontaneously hypertensive (SH) rats to a single dose (3 mg PM/kg body weight or 10 mg PM/kg body weight) of either coarse or fine PM by intratracheal instillation. We assessed changes in biochemical markers, cell differentials, and histopathological changes in the lungs and blood 24 h postexposure. The dose-related adverse effects that both coarse and fine PM induced in the lungs and vascular system were mainly related to cytotoxicity, inflammation, and blood viscosity. We observed clear differences in the extent of these responses to PM from the various locations at equivalent dose levels. There was a trend that suggests that samples from high-traffic sites were the most toxic. It is likely that the toxicological responses of SH rats were associated with specific PM components derived from brake wear (copper and barium), tire wear (zinc), and wood smoke (potassium).

This paper discusses critical issues underlying the interface between air quality science, stakeholder participation, and policy development within the context of the European AIRNET Network multistakeholder project. The paper argues that it is not only the content of air pollution and health issues that stakeholders consider important, but also the process and mechanisms by which the interface operates. A visual representation of the interaction between science, society, and stakeholders in the development, dissemination, and evaluation of effective air quality policy strategies is provided. The paper discusses the role of AIRNET in supporting the Clean Air for Europe (CAFE) program and assesses the AIRNET experience in establishing a network to bridge the gap between air quality policy, stakeholders, the public, and scientific communities.

Within the European Commission-supported thematic network project AIRNET, a stakeholder survey was performed to identify key questions and issues of concern for end users regarding air pollution and health information. On the whole, survey respondents typically asked general questions concerning air pollution and health (i.e., regarding the type of pollutant, emission sources, monitoring, and health impact). Furthermore, an overwhelming response across all stakeholder categories was not the unavailability of information sources to inform policy, but the lack of time available to read and absorb all the information. Overall, the respondents expressed their preference for information that is (1) presented as short and clear overviews, (2) ready for policy use by including a practical linkage between the research findings and implementation of public protection, and (3) in a format easily passed on to others.

To compare the extent and time course of pulmonary injury and repair in 3 rodent species, rats, mice and guinea pigs were continuously exposed for 3, 7, 28, and 56 days to 400 and 800 microg O3/m(3) (0.2 and 0.4 ppm). Recovery from 28 days of exposure was studied at 3, 7, and 28 days after exposure. Pulmonary injury and repair was studied at various time points by histology, electron microscopy, morphometry, and biochemistry. In all 3 species a concentration-related centriacinar inflammation occurred, with a maximum after 3 days of exposure. The number of alveolar macrophages and the pulmonary cell density in the centriacinar region increased progressively until 56 days of exposure, with the guinea pig the most sensitive species. Only the mouse displayed a concentration and exposure-time dependent hypertrophy of bronchiolar epithelium. After 56 days of exposure to 800 microg O3/m(3) in the rat and the guinea pig, giant lamellar bodies in type II cells were present. Exposures for 3 and 7 days at near ambient ozone concentrations (400 microg O3/m(3)) resulted in significantly elevated lung enzyme activities in the mouse, and in significant histological and morphometric changes in all 3 species. In rat and guinea pigs exposures for 56 days resulted in alveolar duct fibrosis. The highest biochemical response and the slowest recovery from ozone exposure were seen in the mouse. Histology, morphometry, and biochemistry revealed a total recovery from a 28-day exposure period in rats after 28 days, while in guinea pigs the ductular septa were still thickened and in mice all enzyme activities were still elevated in comparison with control values. In conclusion, the response of mice to ozone was evaluated as most severe, followed by those of guinea pigs and least in rats.

In this study the effects of inhalatory exposure to coal fly ash on lung pathology and the immune system in rats were examined. Rats were exposed to 0, 10, 30, or 100 mg/m(3) coal fly ash (6 h/day, 5 days/wk) for 4 wk, or to 0 and 100 mg/m(3) for 1 wk, and for 1 wk followed by a recovery in clean air of 3 wk. A concentration-related increase in lung weight was found starting from 30 mg/m(3) coal fly ash. After exposure to 100 mg/m(3), a time-related deposition of free particles in the lungs was observed as well as a time-related number of coal fly ash particles phagocytized in alveolar macrophages. Histological examination revealed increased cellularity in alveolar septa, consisting mainly of mononuclear cell infiltrate, proliferated type II cells, and a slight fibrotic reaction. After a recovery period of 3 wk the histological picture was identical to that after 1 wk of exposure, indicating no significant recovery. No toxicological significant changes were found in the hematological, clinical chemistry, or urine parameters. Effects both on nonspecific defense mechanisms and on specific immune responses were noted. With regard to the immune function in the draining lymph nodes of the lung, a significantly increased number of both T and B lymphocytes was observed. The ratio of both cell types was not changed in either of the groups. In serum of exposed rats a significant increase of up to 150% of the immunoglobulin A (IgA) content was found. The number and phagocytic capacity of macrophages were significantly increased, while the killing of Listeria bacteria per cell ex vivo/in vitro remained unchanged. Natural killer (NK) activity in pulmonary cell suspensions was slightly stimulated in rats exposed for 4 wk to 10 and 30 mg/m(3), whereas an exposure to 100 mg/m(3) resulted in a slight decrease; however, both changes were not significant. In conclusion, the alterations in lung histopathology and immunity, observed in a dose and exposure time relation at concentrations up to and including 100 mg/m(3) coal fly ash, may be considered an adverse response of the host to inhalation of particulate matter. Whether these observed alterations may effect the host resistance must be learned from infection studies.

Capsaicin (8-methyl-N-vanillyl-6-nonenamide) is a widely used tool for the depletion of neuropeptides from sensory C-fibres. Upon capsaicin treatment tachykinins are released, resulting in a variety of responses in the airways. We showed that after capsaicin (0.3 microM; 30 min) treatment of guinea pig tracheal smooth muscle preparations, the maximal contraction of the trachea after methacholine stimulation was strongly increased (capsaicin: 1.147 +/- 0.050 g vs. control: 0.717 +/- 0.047 g). This effect was completely nullified after pretreatment with capsazepine (2-[2-(4-chlorophenyl)ethyl-amino-thiocarbonyl]-7,8-dihydroxy-2,3, 4,5-tetrahydro-1H-2benzazepine; a vanilloid receptor antagonist) and YM38336 (a dual tachykinin NK1 and tachykinin NK2 receptor antagonist). Our results serve as a warning against using capsaicin as a putatively clean pharmacological tool to deplete the neuropeptides from pools on the C-fibres because we showed that capsaicin also strongly influences basal mechanisms in tracheal smooth muscle control.

Proteinase inhibitors may be of potential therapeutic value in the treatment of respiratory diseases such as chronic obstructive pulmonary disease (COPD) or asthma. Our aim was to study the role of neutrophils, and neutrophil-derived serine proteinases in an acute model in patients with asthma. Exposure to ozone induces an acute neutrophilic inflammatory reaction accompanied by an increase in airway hyperresponsiveness. It is thought that these two effects of ozone are linked, and that neutrophil-derived serine proteinases (i.e. elastase) may play a role in the ozone-induced airway hyperresponsiveness. Therefore, we examined the effect of recombinant antileukoprotease (rALP), one of the major serine proteinase inhibitors in the lung, on ozone-induced changes in airway hyperresponsiveness in this model. We observed that 16 h after exposure to ozone, airway hyperresponsiveness to methacholine was increased both following placebo and rALP treatment. There was no significant difference between placebo and rALP treatment (change in area under the dose-response curve to methacholine: 117.3+/-59.0 vs 193.6+/-59.6 % fall x DD; p=.12). Moreover, the immediate decrease in FEV1 after ozone exposure was not significantly different between the two groups (placebo: -29.6+/-6.7%; rALP: -20.9+/-3.8%; p=.11). In addition, no significant differences were observed in plasma levels of fibrinogen degradation products generated by neutrophil serine proteinases before and after exposure to ozone. We conclude that neutrophil-derived serine proteinases are not important mediators for ozone-induced hyperresponsiveness.

We studied the effect of in vivo ozone exposure (3 ppm, 2 h) on methacholine- and histamine-induced guinea pig tracheal smooth muscle contractions in vitro and the role of cyclooxygenase products in this process. After exposure to ozone, methacholine stimulation showed a functional hyperreactivity, whereas after stimulation with histamine a hyporeactivity was observed. These effects could be explained by the release of prostanoids. In a control situation an increase in PGF(2α), PGE(2) and PGD(2) release is observed after stimulation of the histaminergic receptor system. After ozone exposure the release of prostanoids was also enhanced (unstimulated, PGF(2α) and TxB(2); histamine, PGF(2α), PGE(2); methacholine, PGF(2α), TxB(2), 6-kPGF(1α), PGE(2)). This study shows that the prostanoid release is strongly dependent on the receptor system stimulated to induce smooth muscle contraction and the importance of prostanoids in ozone-induced changes in guinea pig tracheal smooth muscle reactivity.

Asthma is an inflammatory disease of the airways, and exacerbations of this disease have been associated with high levels of air pollution. The objective of this study was to examine whether ambient air pollution and/or allergen exposure induces inflammatory changes in the upper airways of asthmatics. Sixty patients with intermittent to severe persistent asthma visited the Hospital's Out Patient Clinic every 2 wk for a period of 3 mo, and on each visit a nasal lavage was obtained. Associations between nasal inflammatory parameters and seasonal allergens and/or air pollution exposures were analyzed using linear regression analysis. The study ran from July 3 to October 6, 1995, during which period ozone (8-h mean: 80 micrograms/m3) and PM10 (24-h mean: 40 micrograms/m3) were the major air pollutants; the major aeroallergen was mugwort pollen (24-h mean: 27 pollen grains/m3). Effects on both cellular and soluble markers in nasal lavage were demonstrated for both ozone and mugwort pollen, but not for PM10. Ambient ozone exposure was associated with an increase in neutrophils (112% per 100 micrograms/m3 increase in 8-h average ozone concentration), eosinophils (176%), epithelial cells (55%), IL-8 (22%), and eosinophil cationic protein (ECP) (19%). Increases in environmental mugwort pollen counts were associated with an increase in nasal eosinophils (107% per 100 pollen/m3) and ECP (23%), but not with neutrophils, epithelial cells, or lL-8. This study demonstrated that both ambient ozone and allergen exposure are associated with inflammatory responses in the upper airways of subjects with asthma, although the type of inflammation is qualitatively different.

The effects of short-term ozone exposure on the lung function and surface activity of surfactant subtypes isolated from rat lung lavage were studied. Rats were exposed to 0.8 ppm ozone for 2 or 12 hr. The surface activity of surfactant was affected by ozone exposure, whereas distinct morphological changes in bronchoalveolar lavage or in the surfactant subtypes were not observed. Adsorption experiments indicated that bronchoalveolar lavage from rats exposed for 12 hr to ozone remained at lower equilibrium surface pressures than lavage from control rats. These observations suggest interference of inflammatory proteins with the surface film. Extracted surfactant, containing only lipids and surfactant proteins B and C, had a decreased adsorption rate after ozone exposure. These results suggest that the activity of one or both of the hydrophobic surfactant proteins (SP-B and SP-C) was affected by ozone.

The effects of acute exposure of guinea pigs to 3 ppm of ozone for 2 h on the receptor density and sensitivity of the muscarinergic-, the histaminergic- and the beta-adrenergic receptor systems were studied, in order to provide more insight in the complex mechanisms underlying the well known ozone-induced changes in receptor functionality. The exposure to ozone did not change either the total amount of receptors present in lung tissue, nor the receptor sensitivity of the systems studied. Although no effects were observed, this does not yet fully exclude the receptor system for being a target of ozone exposure. The receptor function can be changed after exposure to ozone, e.g., the coupling with the G-protein can be influenced. Furthermore, the G-protein itself may have been altered or changes can occur at lower levels in the receptor signal transmission route leading to functional changes after stimulation of the receptor with an agonist.

The acute effects of the inhalation of air polluting agents have been examined by many research groups in both animal models and human beings. For instance, it is evident that exposure to ozone has toxic effects and can lead to lung function disturbances. For this reason it is likely that individuals suffering from COPD or asthma are groups especially at risk with respect to the effects of ozone. The majority of studies dealing with effects of air pollutants on pulmonary allergy are restricted to IgE mediated allergy (type I allergy). Again for ozone, in animal models for type I allergy it has been demonstrated that exposure can affect the induction as well as the effector phase of this type of hyperimmune reaction (e.g. allergic asthma). Recently it has been demonstration in animal models that non-IgE mediated "asthma' T cells, and notably Th1 cells, may play a crucial role. In a murine model it was demonstrated that low molecular weight compounds can induce delayed type hypersensitivity-like reactions in the respiratory tract, and that these reactions are associated with the induction of airway hyperreactivity. Such compounds include toluene diisocyanate (TDI), to which immune responses can be readily mounted, and which can cause occupational asthma through its sensitizing capability, but to which IgE is only detected in a minority of patients suffering from TDI-associated asthma. Effects of air pollutants on Th1 responses in the respiratory tract have not been studied so far. We have demonstrated that ozone can inhibit resistance to a an intratracheal challenge with Listeria monocytogenes, indicating suppression of Th1 immune responses. In addition, we have shown that ozone exposure suppresses pulmonary delayed type hypersensitivity induced by small molecular weight compounds, as well as the tracheal hyperreactivity that is induced during the development of these immune responses, again supporting the hypothesis of suppression of Th1 responses by ozone exposure. These phenomena may be due to activation of Th2 cell dependent reactions that in turn lead to a downregulation of Th1 mediated immunity, or to a direct effect on Th1 cells or other cell types that are crucial for delayed type hypersensitivity and related airway hyperresponsiveness in this model. These data indicate that exposure to air pollutants may have differential consequences on different types of immune responses in the respiratory tract.

We studied the effects of hydrogen peroxide, hypochlorous acid and ozone on muscarinic and beta-adrenergic receptor responses in guinea pig tracheal tissue. Pretreatment of the tracheal strips with hydrogen peroxide (up to 10 mM) did not affect the muscarinic or beta-adrenergic receptor responses after stimulation with methacholine or (-)-isoprenaline respectively. In contrast to hydrogen peroxide, hypochlorous acid (1 mM and 10 mM) decreased the maximal contraction and the pD2-value after stimulation with the muscarinic agonist methacholine. Comparable effects were observed after stimulation with the beta-adrenoceptor agonist (-)-isoprenaline but the beta-adrenoceptor response seemed to be more susceptible to hypochlorous acid treatment than the muscarinic response. In other words, hypochlorous acid changes the balance between muscarinic and beta-adrenergic receptor responses of guinea pig tracheal strips in favour of the muscarinic receptor responses. In vivo exposure of the guinea pigs to 3 ppm ozone for two hours resulted in a hyperreactivity (increase in maximal contraction) after stimulation of the muscarinic receptor with methacholine. No effects were observed in the pD2-value. The beta-adrenergic receptor response was also affected after ozone exposure. No effects were seen in the maximal (-)-isoprenaline induced relaxation but there was an increase (hypersensitivity) in the pD2-value. Our data suggest that oxidative stress modulates receptor responses. Moreover, the type of oxidant seems to differentially affect various receptor responses. This may be of importance to further understand the influence of an oxidative effect (either directly via ozone or through inflammation) in lung tissue.

Rats were exposed to 0.8 ppm ozone for 2 or 12 hr. The latter condition resulted in lung damage and inflammation while the former did not. Directly after exposure surfactant was isolated and two morphologically and functionally different surfactant subtypes were obtained by differential centrifugation. Surfactant subtypes isolated from rats exposed to 0.8 ppm ozone for 2 and 12 hr showed an increase in the amount of heavy subtype and a decrease in light subtype. These results suggest that acute ozone exposure of rats can alter surfactant subtype composition. The conversion in vitro of heavy to light subtype was increased in ozone-exposed rats. Degradation of surfactant protein A (SP-A) was observed during in vitro conversion of heavy subtype isolated from ozone-exposed rats. This suggests that oxidation of SP-A may lead to enhanced susceptibility for degradation. The observed effects were more pronounced in rats exposed for 12 hr than those exposed for 2 hr, indicating that proteolytic enzymes from inflammatory cells may aggravate the observed effects. We conclude that extracellular surfactant metabolism is altered by short-term exposures to ozone and that oxidation of SP-A may contribute to the observed alterations.

Rats and guinea pigs were exposed to 0.8 mg ozone (O3)/m3 (approximately 0.4 ppm) for 12 hr during the daytime, 12 hr during the nighttime, or continuously to investigate circadian variation in O3-induced pulmonary toxicity during single and repeated O3 exposures. Biomarkers in bronchoalveolar lavage (BAL) fluid and lung tissues were measured as indicators of biochemical and inflammatory responses. Nighttime O3 exposure of rats resulted in larger increases of protein, albumin, and inflammatory cells in BAL fluid compared to those after daytime O3 exposure and this daytime-nighttime difference was statistically significant (p < 0.05). Single daytime or nighttime O3 exposure of guinea pigs resulted in comparable increases of BAL fluid proteins and inflammatory cells without a daytime-nighttime difference. Nighttime and continuous O3 exposure of rats for 3 days resulted in comparable increases in lung antioxidant enzyme activities, both of which differed statistically from effects from daytime O3 exposures (p < 0.05). Continuous O3 exposure of guinea pigs for 3 days caused, in general, statistically larger increases in lung tissue parameters compared to nighttime O3 exposures (p < 0.05). These results suggest that the extent of O3-induced acute pulmonary biochemical and inflammatory responses is directly related to the level of physical and respiratory activity. For rats, effects from continuous O3 exposure appear to be controlled by the nighttime, physically active period. In guinea pigs, the comparable responses following daytime or nighttime O3 exposure seem in accordance with their random behavioral daily activity pattern. This study supports the view that physical activity-related increases in inhaled dose significantly enhance the pulmonary O3 responses.

Effects of single (0.4 ppm for 3, 6, or 12 hr) and repeated (0.4 ppm, 12 hr/day for 3 or 7 days) in vivo ozone exposures on rat and mouse alveolar macrophage functions and cell number were investigated. Single ozone exposure of rats resulted in a small (approximately 15%) decrease in Fc-receptor-mediated phagocytosis and phorbol ester-induced superoxide production by the alveolar macrophages and was followed by recovery above control levels within 12 hr of exposure. Repeated exposures of rats for up to 7 days did not alter alveolar macrophage functions, with the exception of the effects of 3 days of exposure on superoxide production (71 +/- 9% as compared with the controls). In mice, significant changes in alveolar macrophage functions were not observed until 12 hr of exposure (at that timepoint phagocytosis was 74 +/- 2%). Repeated ozone exposures of mice did not cause a further decrease in phagocytosis (at Day 7, 74 +/- 14%). Both after 3 and 7 days of repeated ozone exposure of mice, superoxide production by the alveolar macrophages was inhibited approximately 50%. In rats and mice, repeated ozone exposures led to an increase in the number of alveolar macrophages. In mice, this increase appeared at a later time point (at Day 7 vs Day 3) and was less pronounced (at Day 7, 139 +/- 9% vs 179 +/- 17%) as compared with rats. In summary, our data show that rat and mouse alveolar macrophages have different susceptibilities to both single and repeated in vivo ozone exposures.

Phosphatidylcholine (PC) synthesis by alveolar type II cells, as an indicator for the production of pulmonary surfactant, was studied after a 4-h exposure of rats to 4 mg ozone/m3 (2 ppm). Lung ravage fluid analysis after exposure revealed significant increases in proteins, which is indicative for pulmonary injury. When type II cells were isolated immediately and thereafter cultured for 20 h, the rate of PC synthesis in cells derived from ozone-exposed rats was not significantly different from that in cells from unexposed controls. Yet, a decreased rate of PC synthesis was observed when these cells were subsequently exposed to ozone in vitro. The activity of the enzyme glycerolphosphate acyltransferase (GPAT) was slightly enhanced in cultured type II cells isolated from ozone-exposed rats, while the lysophosphatidylcholine acyltransferase (LPCAT) activity was unchanged. However, ozone exposure of rats did result in a significant decrease of PC synthesis when measured in freshly prepared type II cell suspensions, although both GPAT and LPCAT activities were not affected. It is concluded that a decrease in pulmonary surfactant related PC synthesis after ozone exposure of rats can be demonstrated in freshly isolated type II pneumocytes. Cultured type II cells from exposed rats lack this effect and are therefore less useful to study changes in phospholipid biosynthesis after in vivo ozone exposure. The data on in vitro ozone exposure of cultured type II cells, however, support the view that ozone may impair pulmonary surfactant production.

The nature of the rat adipocyte beta-adrenoceptor was studied in further detail using a selected series of tolamol-type beta-adrenoceptor antagonists. Isoprenaline antagonism by these compounds was evaluated on adipocytes, right atrium, left atrium and left hemidiaphragm of the rat. Adipocyte pA2 values were corrected for binding to bovine serum albumin determined separately for each antagonist. A strong correlation between adipocyte and diaphragm pA2 values was found with those antagonists which had an identical N-substituent but a different substitution pattern in the phenoxypropanolamine ring. This relationship was absent with those compounds which had the same 2-methylphenoxypropanolamine moiety but a different N-substituent. With the latter antagonists, however, adipocyte pA2 values correlated significantly with the two cardiac pA2 values. These results support the idea that the interaction site of the rat adipocyte beta-adrenoceptor for the aromatic moiety of arylethanolamines and aryloxypropanolamines has beta 2-characteristics whereas the alkanolamine side-chain interaction site has a beta 1-nature. Finally, it was ascertained that the apparently dualistic (beta 1 and beta 2) character of the rat adipocyte adrenoceptor is not due to the presence of both a beta 1- and a beta 2-receptor population on the fat cell plasma membrane.

The role of enzyme induction in the reduction by acetylsalicylic acid (ASA) of paracetamol-induced hepatic glutathione (GSH) depletion has been studied in rats. Administration of an overdose of paracetamol to control rats resulted in an appreciable decrease of GSH concentration. Pretreatment with the enzyme inducers phenobarbitone, 3-methylcholanthrene (3-MC), pregnenolone-16-alpha-carbonitrile (PCN) and 4,4'-dichlorobiphenyl (4,4'-DCB) significantly potentiated the paracetamol-induced depletion of GSH. Simultaneous administration of an equimolar dose of ASA resulted in a reduction of the paracetamol-induced depletion of GSH in all instances except for those rats that were not pretreated and those given 3-MC. Benorylate, the ASA ester of paracetamol, depressed rat liver GSH to levels comparable to those produced by the combination of paracetamol and ASA. ASA itself caused only minor changes in liver GSH concentrations. The results demonstrate that ASA causes a diminution of paracetamol-induced GSH depletion in rats with phenobarbitone type of enzyme induction. Inhibition of the formation of the reactive metabolite of paracetamol or reduction of the absorption rate of paracetamol seem to be unlikely as mechanisms underlying the ASA-induced effect. An ASA-mediated effect via changes of the hepatic thiol status is proposed.