Beta-adrenergic receptors in psoriasis: evidence for down-regulation in lesional skin

Lesional psoriatic skin displays reduced responsiveness to beta-adrenergic stimulating agents. To elucidate whether the receptor protein itself is responsible for this, lesional and non-lesional psoriatic skin was investigated ex vivo for maximal beta-adrenergic binding density (Bmax) and beta-adrenergic binding affinity (KD). Epidermal crude membrane homogenates (ECMH) were prepared from split-thickness skin biopsies and saturated with the lipophilic beta-adrenergic antagonist (-)-125I-iodocyanopindolol (ICYP) as radioligand. Specific binding was saturable and Scatchard transformation of the binding data revealed a homogeneous class of beta-adrenergic receptors in all nine experiments. The maximal beta-adrenergic binding density was significantly less in lesional than in non-lesional psoriatic skin (Bmax = 49.7 +/- 7.2 fmol/mg protein vs. 67.1 +/- 2.2 fmol/mg protein, n = 9, P < 0.05). The binding affinity was similar in lesional and in non-lesional skin (KD = 9.0 +/- 1.5 pmol/l vs. 8.0 +/- 0.9 pmol/l). These results could at least partially explain the reduced responsiveness of the beta-adrenergic system in lesional psoriatic skin seen after stimulation with beta-adrenergic agonists.