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Competitive inhibition by procaine of carbachol‐induced stimulus‐secretion coupling in rat pancreatic acini
Author(s) -
Ikei Nobuhiro,
Busik Julia,
Habara Yoshiaki,
Kanno Tomio
Publication year - 1993
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.1476-5381.1993.tb13853.x
Subject(s) - procaine , carbachol , chemistry , stimulation , endocrinology , medicine , biophysics , receptor , pharmacology , biochemistry , biology
1 Procaine (0.03–10 m m ) inhibited carbacbol (CCh)‐induced amylase release from rat isolated pancreatic acini in a competitive manner. Kinetic analysis of the relation between CCh concentrations and the amount of amylase released in the presence of various procaine concentrations indicated that procaine caused competitive inhibition with the affinity constant (pA 2 ) value of 5.00 ± 0.08. 2 Receptor binding assay confirmed that procaine (0.01–10 m m ) competitively inhibited [N‐methyl‐ 3 H]‐scopolamine chloride ([ 3 H]‐NMS) binding to its receptor with binding affinity (p K i ) of 4.63 ± 0.10. 3 Procaine transformed CCh‐evoked [Ca 2+ ] i dynamics: the initial rise in [Ca 2+ ] i followed by a gradual decay during continuous stimulation with 3 μ m CCh was transformed by 0.3 m m procaine to the oscillatory [Ca 2+ ] i dynamics, which resembled the response to 0.3 μ m CCh in the absence of procaine. The initial phase of [Ca 2+ ] i oscillation corresponded to the initial phase of CCh‐induced amylase release in isolated perfused acini. 4 Procaine (0.3–3 m m ) did not inhibit the secretory response to cholecystokinin octapeptide (CCK‐8) in isolated incubated acini. A higher concentration of procaine (10 m m ) caused weak but significant inhibition of the response to only limited concentrations of CCK‐8, 30 and 100 p m . Procaine lower than 10 m m was ineffective on [ 125 I]‐BH‐CCK‐8 binding, although procaine (10 m m ) caused weak but significant inhibition of the binding.