PMID- 8575529
OWN - NLM
STAT- MEDLINE
DCOM- 19960314
LR  - 20190624
IS  - 0014-2999 (Print)
IS  - 0014-2999 (Linking)
VI  - 290
IP  - 2
DP  - 1995 Jul 18
TI  - Characterisation of inositol 1,4,5-trisphosphate binding sites in rabbit aortic 
      smooth muscle.
PG  - 145-50
AB  - The present study investigated the characteristics of D-myo-inositol 
      1,4,5-trisphosphate (Ins(1,4,5)P3) binding sites in crude membrane preparations 
      of rabbit aortic smooth muscle. A particular aim was to demonstrate if increases 
      in cytoplasmic cyclic guanosine 3':5' monophosphate (cGMP), which mediates the 
      effect of nitrovasodilators, may cause smooth muscle relaxation in part by the 
      displacement of Ins(1,4,5)P3 binding. Negligible Ins(1,4,5)P3 binding was 
      observed at pH < 7, while maximum binding occurred over the pH range 8-9. 
      Saturation analysis of isotopic dilution binding data revealed an apparently 
      homogenous population of Ins(1,4,5)P3 binding sites with a KD of 4.02 +/- 0.53 nM 
      and a Bmax of 27.7 +/- 4.6 fmol/mg protein. Heparin, an Ins(1,4,5)P3 receptor 
      antagonist, inhibited binding with an IC50 of 11.43 +/- 2.81 micrograms/ml. The 
      ability of other polyphosphate compounds to inhibit Ins(1,4,5)P3 binding in this 
      preparation was also examined. D-myo-Inositol 1,3,4,5-tetrakisphosphate 
      (Ins(1,3,4,5)P4), adenosine 5'-triphosphate (ATP) and guanosine 5'-triphosphate 
      (GTP) inhibited Ins(1,4,5)P3 binding, although each was significantly less potent 
      that Ins(1,4,5)P3. In contrast, cyclic guanosine 3':5' monophosphate (cGMP) did 
      not significantly alter Ins(1,4,5)P3 binding in rabbit aortic smooth muscle. This 
      observation suggests that competitive inhibition of Ins(1,4,5)P3 receptor binding 
      is not an important consideration in cGMP-mediated vascular smooth muscle cell 
      relaxation.
FAU - Murphy, T V
AU  - Murphy TV
AD  - Department of Pharmacology, School of Medical Sciences, University of Bristol, 
      UK.
FAU - Broad, L M
AU  - Broad LM
FAU - Garland, C J
AU  - Garland CJ
LA  - eng
GR  - Wellcome Trust/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Netherlands
TA  - Eur J Pharmacol
JT  - European journal of pharmacology
JID - 1254354
RN  - 0 (Adenine Nucleotides)
RN  - 0 (Calcium Channels)
RN  - 0 (Guanine Nucleotides)
RN  - 0 (Inositol 1,4,5-Trisphosphate Receptors)
RN  - 0 (Ligands)
RN  - 0 (Receptors, Cytoplasmic and Nuclear)
RN  - 85166-31-0 (Inositol 1,4,5-Trisphosphate)
RN  - 9005-49-6 (Heparin)
RN  - H2D2X058MU (Cyclic GMP)
SB  - IM
MH  - Adenine Nucleotides/pharmacology
MH  - Animals
MH  - Aorta/*metabolism
MH  - Calcium Channels/*metabolism
MH  - Cyclic GMP/pharmacology
MH  - Guanine Nucleotides/pharmacology
MH  - Heparin/pharmacology
MH  - Hydrogen-Ion Concentration
MH  - In Vitro Techniques
MH  - Inositol 1,4,5-Trisphosphate/*metabolism
MH  - Inositol 1,4,5-Trisphosphate Receptors
MH  - Ligands
MH  - Muscle, Smooth, Vascular/*metabolism
MH  - Rabbits
MH  - Receptors, Cytoplasmic and Nuclear/*metabolism
EDAT- 1995/07/18 00:00
MHDA- 1995/07/18 00:01
CRDT- 1995/07/18 00:00
PHST- 1995/07/18 00:00 [pubmed]
PHST- 1995/07/18 00:01 [medline]
PHST- 1995/07/18 00:00 [entrez]
AID - 10.1016/0922-4106(95)90027-6 [doi]
PST - ppublish
SO  - Eur J Pharmacol. 1995 Jul 18;290(2):145-50. doi: 10.1016/0922-4106(95)90027-6.