PMID- 11281236
OWN - NLM
STAT- MEDLINE
DCOM- 20010628
LR  - 20190513
IS  - 0895-7061 (Print)
IS  - 0895-7061 (Linking)
VI  - 14
IP  - 3
DP  - 2001 Mar
TI  - Inhibitors of arachidonic acid metabolism have variable effects on calcium 
      signaling pathways.
PG  - 248-53
AB  - The metabolic pathways of arachidonic acid (AA) have been shown to be important 
      in the regulation of cellular function. Several studies have demonstrated both 
      direct and indirect effects of products of these pathways in the regulation of 
      vascular actions, and in particular on signaling pathways. Because intracellular 
      calcium concentration is a significant mediator of stimulus-coupled signal 
      transduction, we investigated the effects of AA pathway inhibitors on angiotensin 
      II (Ang II)-induced calcium mobilization in cultured rat vascular smooth muscle 
      cells (VSMC). Thus, specific calcium pools were examined for differential effects 
      resulting from inhibitors of the three major pathways of AA metabolism. 
      Inhibition of lipoxygenase (LO) with 2.5 micromol/L of 5,8,11 eicosatriynoic acid 
      (ETI), cyclooxygenase (CO) with 2 micromol/L of ibuprofen (IBU), and cytochrome 
      P-450 (P450) with 1 micromol/L of 7-ethoxyresorufin (7ER) all reduced total Ang 
      II-induced intracellular calcium transients ([Ca2+]i) in fura 2-loaded cultured 
      rat VSMC. However, the sites of action affected were unique for each inhibitor. 
      Pretreatment of VSMC with either ETI or IBU inhibited thapsigargin (TG) (1 
      micromol/L)-sensitive calcium increments (control; 118.0 +/- 33.1 nmol/L, n = 9, 
      ETI; 34.7 +/- 4.8 nmol/L, n = 9, IBU; 40.3 +/- 8.8 nmol/L, n = 8, P < .05 v 
      control). Both caffeine (CAF) and ryanodine (RY) treatment attenuated Ang 
      II-induced [Ca2+]i; however, pretreatment with ETI, IBU, or 7ER did not alter 
      this effect. In other studies, the LO inhibitor ETI attenuated Ang II-induced 
      Ca2+ influx, whereas inhibitors of CO and P450 pathways had no effect. These data 
      show that 1) E
FAU - Kanda, H
AU  - Kanda H
AD  - Department of Veteran's Affairs Greater Los Angeles Healthcare System, Sepulveda, 
      California 91343, USA.
FAU - Hori, M T
AU  - Hori MT
FAU - Golub, M S
AU  - Golub MS
FAU - Tuck, M L
AU  - Tuck ML
LA  - eng
GR  - R01-HL41295/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Am J Hypertens
JT  - American journal of hypertension
JID - 8803676
RN  - 0 (Cyclooxygenase Inhibitors)
RN  - 0 (Cytochrome P-450 Enzyme Inhibitors)
RN  - 0 (Lipoxygenase Inhibitors)
RN  - 0 (Oxazines)
RN  - 15662-33-6 (Ryanodine)
RN  - 27YG812J1I (Arachidonic Acid)
RN  - 3G6A5W338E (Caffeine)
RN  - 5725-91-7 (ethoxyresorufin)
RN  - FC398RK06S (8,11,14-Eicosatrienoic Acid)
RN  - JQS194YH3X (mead acid)
RN  - SY7Q814VUP (Calcium)
RN  - WK2XYI10QM (Ibuprofen)
SB  - IM
MH  - 8,11,14-Eicosatrienoic Acid/*analogs & derivatives/*pharmacology
MH  - Animals
MH  - Arachidonic Acid/*metabolism
MH  - Caffeine/pharmacology
MH  - Calcium/physiology
MH  - Calcium Signaling/*drug effects
MH  - Cells, Cultured
MH  - Cyclooxygenase Inhibitors/*pharmacology
MH  - *Cytochrome P-450 Enzyme Inhibitors
MH  - Ibuprofen/*pharmacology
MH  - Lipoxygenase Inhibitors/*pharmacology
MH  - Male
MH  - Muscle, Smooth, Vascular/metabolism
MH  - Oxazines/*pharmacology
MH  - Rats
MH  - Ryanodine/pharmacology
EDAT- 2001/04/03 10:00
MHDA- 2001/06/29 10:01
CRDT- 2001/04/03 10:00
PHST- 2001/04/03 10:00 [pubmed]
PHST- 2001/06/29 10:01 [medline]
PHST- 2001/04/03 10:00 [entrez]
AID - S0895-7061(00)01270-X [pii]
AID - 10.1016/s0895-7061(00)01270-x [doi]
PST - ppublish
SO  - Am J Hypertens. 2001 Mar;14(3):248-53. doi: 10.1016/s0895-7061(00)01270-x.