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Ontogeny of β‐adrenergic desensitization in rabbit tracheal smooth muscle
Author(s) -
Omlor Gregory J.,
Quinn Lisa M.,
Schramm Craig M.
Publication year - 1996
Publication title -
pediatric pulmonology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.866
H-Index - 106
eISSN - 1099-0496
pISSN - 8755-6863
DOI - 10.1002/(sici)1099-0496(199610)22:4<255::aid-ppul5>3.0.co;2-l
Subject(s) - desensitization (medicine) , homologous desensitization , agonist , endocrinology , medicine , bronchodilation , methacholine , pharmacology , receptor , bronchodilator , asthma , respiratory disease , lung
Prolonged or repeated exposure to β‐agonist medications may result in a desensitization of the agonist‐mediated response. Under certain conditions, such agonist‐induced desensitization may limit the efficacy of administered β‐adrenergic agonists to elicit bronchodilation. Accordingly, the present study was designed to study the mechanisms of acute β‐adrenergic desensitization in maturing rabbit tracheal smooth muscle (TSM). Isometric tension was measured in tracheal ring segments isolated from newborn and mature rabbits and half‐maximally contracted with Methacholine (Meth) or KCl. TSM segments were serially relaxed with repetitive single doses of isoproterenol (ISO: 0.1, 1.0, 10, or 100 μM) or prostaglandin E 2 (PGE 2 : 0.1 or 10 μM). Serial administration of ISO‐elicited dose‐dependent desensitization of relaxation in mature and newborn TSM, contracted with either Meth or KCl. In contrast, the relaxant response to PGE 2 was retained in the ISO‐desensitized tissue. Repeated administration of PGE 2 elicited no desensitization of PGE 2 responsiveness, but did induce some dose‐dependent desensitization of the ISO response in mature TSM. Compared to mature tissues, newborn TSM developed subtotal desensitization to 100 μM ISO and no ISO desensitization in response to PGE 2 . Thus, these findings demonstrate that (1) β‐adrenoceptor responsiveness undergoes dose‐dependent homologous and, to a lesser extent, heterologous desensitization in rabbit TSM; and (2) both β‐adrenergic desensitization mechanisms increase with postnatal maturation. Pediatr Pulmonol. 1996; 22:255–262. © 1996 Wiley‐Liss, Inc.