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DIFFERENTIAL EFFECT OF LITHIUM ON f1-ADRENOCEPTOR DOWN-REGULATION IN LYMPHiOBLAST CELL LINES FROM PATIENTS WITH BIPOLAR DEPRESSION AND HEALTHY CONTROL SUBJECTS G. Kay * & J.M. Elliott, Department of Pharmacology, St. Mary's Hospital Medical School, London, W2 1PG. Abnormalities of adrenergic function have been postulated as a biochemical basis for affective disorders (Werstiuk et al, 1990). Lymphoblast cell lines provide a useful model of human beta-adrenergic receptor (M-AR) function. A reduced a-AR number has been shown in lymphoblasts from patients with bipolar depression (BP) (Wright et al ,1984), but this was not seen by Berrettini et al (1987). We have previously shown that chronic coincubation with isoprenaline causes time and concentration dependent down-regulation of lymphoblast 13-ARs (Kay & Elliott, 1988), with a parallel desensitization of the cAMP response (Kay & Elliott, 1990). In this study we have investigated lymphoblast [-AR number and down-regulation in BP patients and the effects of lithium on these parameters. Cell lines from 9 subjects with bipolar depression (BP) and 9 sex and age matched controls were established. Confluent cells were coincubated with or without lmM lithium chloride for 7 days and with or without lnM isoprenaline for 24 hours prior to assay. Coincubations were stqged by centrifugation and the cells disrupted by homogenisation and sonication. The radioligand binding assay was carried out using [ I]-iodocyanopindolol, a VAR antagonist, as previously described (Kay & Elliott, 1988). There was no difference in the basal [-AR binding capacity between BP cell lines and control cell lines (Table 1). However coincubation with isoprenaline caused a down-regulation of [-AR number by 40±5% in control cell lines, whereas in BP cell lines the down-regulation was only 10±12%. This difference was significant by Student's unpaired t-test (P
DIFFERENTIAL EFFECT OF LITHIUM ON f1-ADRENOCEPTOR DOWN-REGULATION IN LYMPHiOBLAST CELL LINES FROM PATIENTS WITH BIPOLAR DEPRESSION AND HEALTHY CONTROL SUBJECTS G. Kay * & J.M. Elliott, Department of Pharmacology, St. Mary's Hospital Medical School, London, W2 1PG. Abnormalities of adrenergic function have been postulated as a biochemical basis for affective disorders (Werstiuk et al, 1990). Lymphoblast cell lines provide a useful model of human beta-adrenergic receptor (M-AR) function. A reduced a-AR number has been shown in lymphoblasts from patients with bipolar depression (BP) (Wright et al ,1984), but this was not seen by Berrettini et al (1987). We have previously shown that chronic coincubation with isoprenaline causes time and concentration dependent down-regulation of lymphoblast 13-ARs (Kay & Elliott, 1988), with a parallel desensitization of the cAMP response (Kay & Elliott, 1990). In this study we have investigated lymphoblast [-AR number and down-regulation in BP patients and the effects of lithium on these parameters. Cell lines from 9 subjects with bipolar depression (BP) and 9 sex and age matched controls were established. Confluent cells were coincubated with or without lmM lithium chloride for 7 days and with or without lnM isoprenaline for 24 hours prior to assay. Coincubations were stqged by centrifugation and the cells disrupted by homogenisation and sonication. The radioligand binding assay was carried out using [ I]-iodocyanopindolol, a VAR antagonist, as previously described (Kay & Elliott, 1988). There was no difference in the basal [-AR binding capacity between BP cell lines and control cell lines (Table 1). However coincubation with isoprenaline caused a down-regulation of [-AR number by 40±5% in control cell lines, whereas in BP cell lines the down-regulation was only 10±12%. This difference was significant by Student's unpaired t-test (P
