モルモット肺における Direct β-Adrenergic Receptor Assay

α, β受容体遮断剤投与の影響について

抄録

The lung is one of the organs that possess abundant β-adrenergic receptors. Direct radiologic binding methods for studying β-adrenergic receptors have been developed recently. These methods can provide new insights into the molecular characteristics and regulatory properties of β-adrenergic receptors in the lung.
Recently, α-adrenergic receptor blockers have been used for the therapy of brochial asthma and some good theraeputic effects have been reported. However the mechanisms have not been elucidated yet.
β-adrenergic receptor blockers are widely used for patients with hypertension or ischemic heart diseases, and sometimes the use of β-adrenergic receptor blockers elicits asthmatic attacks in patients with bronchial asthma. But actually the incidence of such attacks is not so high as could be expected.
In the present investigation we determined the number of β-adrenergic receptors in the lung membrane of guinea-pigs, weighing 150-280g. by direct methods using [³H]-(-)-dihydroalprenolol ([³H]-DHA). Effects of phentolamine and propranolol on the β-adrenergic receptors in the lung were also investigated.
1) The mean values and standard deviation of the number of β-adrenergic receptors (the concentration of [³H]-DHA binding sites) and the dissociation constant (Kd) were 789±121f mol/mg protein and 1.14±0.22nM, respectively (n=10).
2) The treatment of guinea-pigs with phentolamine (1mg/kg, subcutaneously, for 6 days) induced a significant increase in the number of lung β-adrenergic receptors, 971±149fmol/mg protein (n=8, p<0.02), while Kd did not show any significant change. This increase in the number of lung β-adrenergic receptors might be one of the mechanisms of α- adrenergic receptor blockers in bronchial asthma.
3) The treatment of guinea-pigs with propranolol (1mg/kg, subcutaneously, for 6 days) induced a significant increase in the number of lung β-adrenergic receptors, 931±141fmol/mg protein (n=8, p<0.05), while Kd did not show any significant change. This increase in the number of lung β-adrenergic receptors might be one of the reasons why the incidence of asthmatic attacks is not so high in spite of the widespread use of β-adrenergic receptor blockers.