The selectivity of ß-blockers for the human ß1- and ß2- adrenoceptors G.Baker, I.P.Hall & S.J.Hill. Institute of Cell Signalling, Queen's Medical Centre, Nottingham NG7 2UH, UK.

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ß-adrenoceptor antagonists are a widely used class of drugs in clinical practice e.g. in the treatment of hypertension, ischaemic heart disease, anxiety, migraine and glaucoma (Andersson & Vinge, 1990; Hampton 1994; Stamper et al., 2002). However, for most cardiovascular uses, ßl selective drugs are preferable to minimise respiratory side effects. The aim of this study was to determine the selectivity of a range of clinically-used beta-blockers for binding to cell surface human ß1 and ß2 adrenoceptors.

CHO-K1 cells lines stably expressing either the human ß1- (ß1-AR at 1100 fmol/mg protein, Baker et al., 2003) or human ß2- (ß2-AR at 400 fmol/mg protein, Baker et al, 2002) adrenoceptor were used. ³H-CGP 12177 binding to whole cells was performed in 96 well white view plates as described previously (Baker et al., 2003). Log K_D values for each beta-blocker were determined from inhibition of the specific binding of 0.3 nM ³H-CGP 12177. Non-specific binding was determined with 100nM ICI 118551 (ß2-AR) or 100nM (CGP20712A (ß1-AR).

The results (see Table) show that although CGP 20712A and ICI 118551 were very selective (CGP 20712A 503 fold for the ß1-AR, ICI 118551 489 fold for ß2-AR), the majority of clinically used beta-blockers showed very little selectivity between the two human b-adrenoceptors.

Table showing the log K_D values (mean ±s.e.m.) for a range of ß-blockers obtained from whole cell binding at the human ß1-AR and ß2-AR. n = number of separate experiments. Selectivity ratio is the K_D at the ß1-AR divided by that for ß2-AR. Thus a value of 1.0 shows equal affinity for the two receptors, values greater than one reflect ß1-AR selectivity and those below one reflect ß2-AR selectivity.

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JGB holds a Wellcome Trust Clinical Training Fellowship