Difference between lung and spleen susceptibility of beta-adrenergic receptors to desensitization by terbutaline.
There are many reports about a marked down-regulation of beta-adrenergic receptors by beta agonists in human leukocytes. To determine whether beta receptors in lung tissue are down regulated by the long-term administration of beta agonists, as are those in the spleen (which consists largely of lymphocytes), we injected terbutaline (0.1 mg/kg, t.i.d.) intramuscularly into rats for either 3 or 6 days. We observed a significant decrease in beta-receptor density in spleen tissue but not in lung parenchyma, associated with terbutaline injection. The affinity for an antagonist did not change significantly in any group in either tissue. We did not observe any change in alpha 1-adrenergic receptors in the lung after this treatment. In in vitro studies, we also observed reduced beta-receptor density in spleen cells but not in lung parenchyma after incubation of these tissues with terbutaline. However, there was agonist-specific alteration in lung beta receptors. It was found that the isoproterenol competition curve for 3H-dihydroalprenolol binding shifted to the right and steepened, suggesting reduced affinity of the receptors for isoproterenol. We used whole lung and did not examine bronchial smooth muscle per se, nor were functional studies performed. Our results show a difference between lung parenchyma and spleen tissue in the susceptibility of beta receptors to desensitization by an adrenergic agonist and suggest that there may be such a difference in sensitivity between beta receptors in human lung and leukocytes.
D000818:Animals; D002478:Cells, Cultured; D004082:Dihydroalprenolol / Q000378:metabolism; D006801:Humans; D007545:Isoproterenol / Q000378:metabolism; D008168:Lung / Q000187:drug effects* / Q000502:physiology; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D011941:Receptors, Adrenergic / Q000187:drug effects*; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects; D011943:Receptors, Adrenergic, beta / Q000187:drug effects* / Q000502:physiology; D013154:Spleen / Q000187:drug effects* / Q000502:physiology; D013726:Terbutaline / Q000494:pharmacology*
D011941:Receptors, Adrenergic; D011942:Receptors, Adrenergic, alpha; D011943:Receptors, Adrenergic, beta; D004082:Dihydroalprenolol; D007545:Isoproterenol; D013726:Terbutaline