Abstract：
:Guinea pig gallbladder muscle strips were used to investigate the contribution of different sources of diacylglicerol (DAG) in the cholecystokinin (CCK)-induced contraction. The involvement of arachidonic acid (AA) in this response was also investigated. Three distinct pathways for DAG production were investigated with specific phospholipase (PL) inhibitors. U-73122 (10 microM) was used for inhibition of phosphoinositide-specific-PLC (PI-PLC), D-609 (100 microM) for phosphatidylcholine specific-PLC (PC-PLC), and propranolol (100 microM) for phospholipase D (PLD). Separate or combined inhibition of each of these enzymes showed that the CCK-induced output of DAG involves the parallel activation of each of these phospholipases. Thus, after inhibition of a PL subtype, the remaining subtypes were able to functionally compensate in mediating CCK-induced contraction. Inhibition of AA production via DAG-lipase or phospholipase A(2) (PLA(2)) was accomplished using RHC-80267 (40 microM), mepacrine (100 microM) and 4-BPB (100 microM). These inhibitors diminished contractile response, indicating that AA is an important modulator of CCK-induced contraction. Indomethacin (10 microM) and nordihydroguaiaretic acid (NDGA, 100 microM), which inhibit subsequent steps in AA metabolism through the cyclooxygenase and 5-lipooxygenase pathways, also inhibited contractions. Taken together, these results show that CCK redundantly activates PC-PLC, PI-PLC and PLD, to produce DAG, which in turn stimulates PKC and provides a substrate for the generation of AA. sPLA(2) is also a source of AA, whose metabolites are, in part, responsible for determining the magnitude of the CCK-evoked contraction.
journal_name
Biochem Pharmacoljournal_title
Biochemical pharmacologyauthors
Alcón S,Morales S,Camello PJ,Pozo MJdoi
10.1016/s0006-2952(02)01259-5subject
Has Abstractpub_date
2002-10-01 00:00:00pages
1157-67issue
7eissn
0006-2952issn
1873-2968pii
S0006295202012595journal_volume
64pub_type
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