The tissue distribution of the human b b 3 -adrenoceptor studied using a monoclonal antibody: Direct evidence of the b b 3 -adrenoceptor in human adipose tissue, atrium and skeletal muscle 2,3 The human b 3 -adrenoceptor was later cloned by Emorine et al. 4 The pharmacology of the cloned b 3 -adrenoceptor agreed with the pharmacological data previously obtained in rodent adipose tissue, gut, and skeletal muscle in that the badrenoceptors in these tissues were insensitive to classical b-adrenoceptor antagonists such as propranolol.5 ± 8 Aryloxypropanolamine b 1 ab 2 adrenoceptor antagonists, exempli®ed by CGP12177, evoke a lipolytic response in rat adipose tissue through agonism at b 3 -adrenoceptors. 9 Similarly, selective b 3 -adrenoceptor agonists, such as BRL-37344, showed similar or greater potency than isoproterenol in stimulating lipolysis, but were much less potent than isoproterenol in stimulating responses mediated by b 1 -or b 2 -adrenoceptors. 10 The assessment of the pharmacological role of b 3 -adrenoceptors in human tissues has proved more controversial. For example, lipolysis in human white adipocytes induced by isoproterenol is sensitive to propranolol.11 Also, CGP12177-induced lipolytic responses have been demonstrated by some 12 ± 14 but not others. 9,15 It is now evident from comparisons of cloned human and rat b 3 -adrenoceptors that there are signi®cant species differences in pharmacology. 16 Attempts to detect b 3 -mRNA in human tissues using reverse-transcription PCR have also given conicting results. Krief et al 17 detected b 3 -adrenoceptor mRNA in several tissues, including gall bladder, adipose tissue and colon, while Thomas and Liggett 18 failed to detect a b 3 -adrenoceptor signal. Recently, RNAase protection assays, that do not rely on ampli®cation techniques, were used to identify b 3 -adrenoceptor mRNA in a variety of human tissues, including

A decision-making style characterized by a drive to avoid potential loss rather than to seek possible reward may help decision making for ASD in some situations, but ultimately hinder functioning in relation to prosocial engagement and other complex situations where gain rather than punishment is the most effective motivating factor.

SummaryA hybrid plasminogen activator consisting of the “A” chain of plasmin linked to the “B” chain of rt-PA was inhibited in vitro in human and guinea pig plasmas 4 to 5-fold more rapidly than its parent activator, two-chain t-PA. Using zymographic and autoradiographic techniques together with the use of immunodepleted plasma the major inhibitor was identified as aIpha-2-antiplasmin. The pharmacokinetic profile of the hybrid in guinea pigs was determined by two different methods: disappearance of fibrinolytic activity and removal of radiolabelled hybrid from the circulation. Fibrinolytic activity was cleared rapidly via inhibitory mechanisms, whilst radiolabelled material was cleared considerably more slowly due to the formation of hybrid-inhibitor complexes. When the active site of the hybrid was reversibly acylated inhibitory mechanisms were evaded and a prolonged pharmacokinetic profile of activity was observed.

An acylated, recombinant plasminogen/t-PA hybrid has sufficiently slow clearance to be administered by bolus and is more potent and fibrin selective than t-PA in vivo.

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