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Selective activation by photodynamic action of cholecystokinin receptor in the freshly isolated rat pancreatic acini
Author(s) -
An Yu Ping,
Xiao Rui,
Cui Hong,
Cui Zong Jie
Publication year - 2003
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.0705295
Subject(s) - bethanechol , cholecystokinin , cholecystokinin receptor , chemistry , muscarinic acetylcholine receptor , endocrinology , medicine , atropine , receptor , biology , biochemistry
Sulphonated aluminium phthalocyanine (SALPC) photodynamic action induces amylase secretion and permanent calcium oscillation in rat pancreatic acinar cells, because of the activation of phospholipase C or signalling proteins upstream. The aim of the present study was to investigate the involvement of muscarinic acetylcholine and cholecystokinin (CCK) receptors. Muscarinic receptor antagonist atropine (10 μ M ) blocked amylase secretion induced by bethanechol (100 μ M ), and CCK 1 receptor antagonist ( S )‐ N ‐[1‐(2‐fluorophenyl)‐3,4,6,7‐tetrahydor‐4‐oxo‐pyrrolo‐[3,2,1‐jk][1,4] benzodiazepine‐3yl]‐1H‐indole‐2‐carboxamide (FK480) (1 μ M ) blocked amylase secretion induced by CCK (100 p M ). Amylase secretion induced by SALPC photodynamic action was not inhibited when atropine and FK480 were present during photodynamic action. However, addition of FK480 1 μ M after initiation of photodynamic action inhibited photodynamic amylase secretion. Bethanechol (10, 100 μ M ) added after photodynamic action resulted in a full secretory response. Atropine (10 n M ) abolished calcium oscillation induced by bethanechol (5 μ M ), and FK480 (10 n M ) blocked calcium oscillation induced by CCK (10 p M ). Atropine up to 10 μ M was without effect on Ca 2+ oscillation triggered by photodynamic action, but these oscillations were abolished by FK480 (10 n M ). FK480 (10 n M ) had no effect on calcium oscillations induced by bethanechol (5 μ M ). Bethanechol 5 μ M , added after FK480 blockade of photodynamic calcium oscillation, still triggered regular calcium oscillation. It is concluded that SALPC photodynamic action selectively and permanently activates CCK receptor in rat pancreatic acini. Such permanent and selective modulation of signalling proteins has important implications for the treatment of pancreatitis, prion diseases, and neurodegenerative disorders.British Journal of Pharmacology (2003) 139 , 872–880. doi: 10.1038/sj.bjp.0705295