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The effect of the protein phosphatases inhibitor cantharidin on β‐adrenoceptor‐mediated vasorelaxation
Author(s) -
Knapp Jörg,
Bokník Peter,
Linck Bettina,
Luss Hartmut,
Müller Frank U.,
Neumann Peter Nacke Joachim,
Vahlensieck Ute,
Schmitz Wilhelm
Publication year - 1997
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.0700929
Subject(s) - cantharidin , ibmx , phosphodiesterase , phosphodiesterase inhibitor , chemistry , stimulation , medicine , endocrinology , pharmacology , biology , biochemistry , enzyme , forskolin , organic chemistry
1 Cantharidin, an inhibitor of protein phosphatase types 1 (PP1) and 2A (PP2A), increased basal tone of bovine isolated coronary artery rings (CARs) with and without endothelium in a time‐and concentration‐dependent manner with pEC 50 values of about 5.1 and 5.2, respectively, for both preparations. 2 β‐Adrenoceptor stimulation with isoprenaline (Iso; 0.03–100 μm) or inhibition of phosphodiesterase activity by 3‐isobutyl‐l‐methylxanthine (IBMX; 10–1000 μm), respectively, relaxed CARs precontracted with KC1 (75 mm). CARs with and without endothelium showed no difference in the relaxing response to Iso and IBMX, respectively. 3 Cantharidin (3 μm) attenuated vasorelaxation induced by Iso (0.03–100 μm) in CARs with and without endothelium in a time‐dependent manner, whereas vasorelaxation induced by IBMX (10–1000 μm) was not attenuated by 3 μM cantharidin. 4 Cantharidin (3 μm) did not affect cyclic AMP content in bovine cultured vascular cells, i.e. coronary artery smooth muscle cells (BCs), aortic endothelial cells (BAECs) and aortic smooth muscle cells (BASMCs), either under basal conditions, after β‐adrenoceptor stimulation (Iso) or inhibition of phosphodiesterase activity (IBMX), respectively. 5 Cantharidin inhibited protein phosphatase activity in homogenates from bovine coronary artery rings with a pIC 50 of about 6.0. In homogenates of bovine cultured vascular cells pIC 50 values of cantharidin amounted to about 6.5 for BCs, 6.7 for BAECs and 6.7 for BASMCs, respectively. 6 It was concluded that cantharidin differently affects vasorelaxation due to stimulation of [3‐adrenoceptors (Iso) or inhibition of phosphodiesterase activity (IBMX), respectively. The attenuation of β‐adrenoceptor‐mediated vasorelaxation by phosphatase inhibition is not due to diminished adenosine 3′: 5′‐cyclic monophosphate (cyclic AMP) generation but could be evidence for different subcellular compartments of cyclic AMP.