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The effect of M&B 22948 on methacholine‐ and histamine‐induced contraction and inositol 1,4,5‐trisphosphate levels in guinea‐pig tracheal tissue
Author(s) -
Langlands John M.,
Rodger Ian W.,
Diamond Jack
Publication year - 1989
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1989.tb12600.x
Subject(s) - histamine , methacholine , endocrinology , medicine , contraction (grammar) , guinea pig , chemistry , phosphodiesterase , inositol , stimulation , biology , receptor , biochemistry , lung , enzyme , respiratory disease
The effect of a cyclic GMP phosphodiesterase inhibitor, M&B 22948, on methacholine‐ and histamine‐induced contraction and inositol 1,4,5‐trisphosphate (IP 3 ) elevation was studied in guinea‐pig tracheal rings. After addition of methacholine or histamine the rise in IP 3 content was rapid and transient reaching a maximum after 5–15 s, which coincided with the maximum rate of tension development. Cyclic GMP levels of the tissue were elevated by M&B 22948 before agonist stimulation and further elevated by addition of methacholine or histamine. Cyclic AMP levels were not altered by any of these agents. M&B 22948 abolished IP 3 generation induced by methacholine or histamine, but did not alter the rate or magnitude of tension development. Thus, IP 3 generation does not appear to be responsible for the contractions induced by methacholine or histamine in this tissue.