Premium
Mechanism underlying histamine‐induced desensitization of amylase secretion in rat parotid glands
Author(s) -
Eguchi Takafumi,
Ishikawa Yasuko,
Ishida Hajime
Publication year - 1998
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 - 10.1038/sj.bjp.0701981
Subject(s) - histamine , okadaic acid , pertussis toxin , histamine h2 receptor , histamine h4 receptor , cholera toxin , histamine receptor , medicine , endocrinology , receptor , biology , histamine h1 receptor , secretion , gs alpha subunit , g protein , chemistry , phosphatase , biochemistry , phosphorylation , antagonist
1 Histamine acted on H 2 receptors in rat parotid tissues and induced the amylase secretion. Immunoblot analysis by using anti‐H 2 receptor protein antiserum demonstrated that histamine induced the increase and decrease in the amounts of H 2 receptor proteins in basolateral and intracellular membranes, respectively. 2 Short‐term treatment with histamine resulted in decreases in amylase secretion, the density of H 2 receptors and their affinity for the agonists during further incubation with histamine, but showed an unaltered secretory response to isoproterenol, indicating that the histamine‐induced desensitization was confined to H 2 receptors. 3 This treatment triggered a 20% decrease in the histamine‐stimulated adenylate cyclase activity and a 40% decrease in the phosphorylation level of Gi2α protein in the tissues, resulting in an increase in pertussis toxin (IAP)‐catalyzed ADP‐ribosylation of the protein. An enhancement of cholera toxin‐catalyzed ADP‐ribosylation of Gs protein was observed only during the first incubation with histamine. 4 This treatment triggered a 30% decrease and a 60% increase in the histamine‐stimulated activities of protein kinase A and protein phosphatase 2A in the tissues, respectively. 5 Pretreatment with okadaic acid completely blocked the histamine‐induced decrease in amylase secretion and increase in IAP‐catalyzed ADP‐ribosylation of Gi protein. The levels of Gi2α and Gsα proteins in the tissues were not modified by histamine treatment and the level of Gi2α protein was not affected by pretreatment with okadaic acid, as assessed by immunoblot analyses with anti‐Gi2α and anti‐Gsα protein antiserum. 6 The regulation of Gi2α protein phosphorylation in parotid tissues plays an important role in the histamine‐induced desensitization of amylase secretion.British Journal of Pharmacology (1998) 124 , 1523–1533; doi: 10.1038/sj.bjp.0701981