1 The agonist-speci®c coupling properties of the three cloned human a 2 -adrenoceptor subtypes have been compared, when expressed at similar levels in Chinese hamster ovary (CHO) cell lines, using noradrenaline and (+)-meta-octopamine as agonists. 2 Noradrenaline can couple the receptor to both the inhibition and stimulation of forskolinstimulated cyclic AMP production in all three receptor subtypes, with the relative strength of the coupling to the pathways varying for each of the receptor subtypes. 3 meta-Octopamine selectively couples the a 2A -adrenoceptor only to the inhibition of forskolinstimulated cyclic AMP production. However, meta-octopamine couples the a 2B -and a 2C -adrenoceptors to both the inhibition and stimulation of forskolin-stimulated cyclic AMP production. 4 The relative potency of meta-octopamine to noradrenaline varies between the di erent a 2 -adrenoceptor subtypes. The e ects of meta-octopamine are around two orders of magnitude less potent than those of noradrenaline on both the a 2A -and a 2B -adrenoceptor subtypes. In contrast, in the case of the a 2C -adrenoceptor, meta-octopamine is only one order of magnitude less potent than noradrenaline in the stimulation of forskolin-stimulated cyclic AMP production and, in addition, is equipotent with noradrenaline in the inhibition of forskolin-stimulated cyclic AMP production and has an increased maximal response. This raises the possibility that meta-octopamine may have physiologically important actions via a 2C -adrenoceptors in vivo. 5 The results show that the modulation of cyclic AMP production occurs in both a subtype-and agonist-speci®c manner for a 2A -adrenoceptors and in a subtype speci®c manner for a 2B -and a 2C -adrenoceptors.

Cochrane reviews v industry supported meta-analyses We should read all reviews with caution Editor-That industry sponsored metaanalyses differ in conclusions from Cochrane reviews does not mean that industry sponsorship is the only source of bias or that Cochrane reviews should be uncritically accepted. 1 Allegiances of authors of meta-analyses are not only associated with selective attention to relevant studies and more positive conclusions in the case of industry ties. 2 We should be sceptical about a comparative review from the director of a Cochrane Centre that puts the centre in such a favourable light. Cochrane reviews are sometimes conducted on literature that is not ready for meta-analysis, with adverse implications for clinical practice and public policy. A recent Cochrane meta-analysis concluded that couples therapy was not better than individual therapy for depression. 3 The offering of couples therapy should be a matter of "patient preference and availability of specific resources." Yet, the studies reviewed were all seriously flawed. None had close to the minimal cell size necessary for inclusion in a meta-analysis, much less for a nonequivalence trial. Such a premature conclusion serves to discourage the commitment of scarce resources to having marital therapists available or to research providing an adequate comparison between the two forms of therapy. Whether the Cochrane Collaboration is free of bias should not be left to the collaboration to decide. Bjordal et al showed that only investigators associated with negative findings had been recruited to the review group for a Cochrane report on low level laser therapy in osteoarthritis. 4 The review had numerous deficiencies in ways consistently supporting its negative conclusion. The Cochrane Collaboration describes itself as "the gold standard in evidence-based healthcare" (www3.interscience.wiley. com/cgi-bin/mrwhome/ 106568753/HOME). The paragraph in This week in the BMJ for the paper by Jørgensen et al admonished us to "Read industry supported drug reviews with caution." This should be expanded to all reviews, including those of the Cochrane Collaboration.

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