PMID- 7611401
OWN - NLM
STAT- MEDLINE
DCOM- 19950815
LR  - 20171213
IS  - 0002-9513 (Print)
IS  - 0002-9513 (Linking)
VI  - 268
IP  - 6 Pt 1
DP  - 1995 Jun
TI  - Ryanodine-induced calcium release from hepatic microsomes and permeabilized 
      hepatocytes.
PG  - G1017-24
AB  - Inositol 1,4,5-trisphosphate [Ins(1,4,5)P3] is a second messenger that releases 
      Ca2+ from hepatocyte microsomes. The toxic alkaloid ryanodine modulates Ca2+ 
      release via a receptor (RyR) identified in a variety of cell systems, but its 
      regulation and functional significance in liver are undefined. Similarly, the 
      role in hepatocyte Ca2+ regulation of adenosine 5'-cyclic diphosphate-ribose 
      (cADPR), which is the putative endogenous ligand for RyR in other cell systems, 
      has not been defined. Utilizing microsomes and permeabilized cells, we have 
      investigated Ca2+ regulation in hepatocytes and, in particular, effects of 
      ryanodine, cADPR, and other putative modulators on Ca2+ release and compared 
      these with Ins(1,4,5)P3-induced Ca2+ release. Ryanodine at > or = 50 microM 
      released 20% of microsomal Ca2+, and, in contrast to Ins(1,4,5)P3, no 
      potentiation was observed with guanosine 5'-triphosphate and polyethylene glycol. 
      Ins(1,4,5)P3-induced Ca2+ release was demonstrable after maximal 
      ryanodine-induced Ca2+ release, suggesting that distinct Ca2+ stores are 
      involved. cADPR (5 microM) did not induce Ca2+ release, alone or in combination 
      with calmodulin or hepatic cytosol, nor did it influence ryanodine-induced 
      release, in microsomes or permeabilized hepatocytes (in which ryanodine released 
      25% of the sequestered Ca2+). Ryanodine-induced Ca2+ release in microsomes was 
      not influenced by 20 mM caffeine, which itself did not mobilize Ca2+, but was 
      prevented by 500 microM tetracaine, which was shown to induce Ca2+ release. We 
      conclude that ryanodine is capable of mobilizing Ca2+ in the hepatocyte from 
      microsomal stores that are distinct from those that can be regulated by 
      Ins(1,4,5)P3 but that cADPR has no such effect. These data suggest that cADPR 
      does not serve as the endogenous ligand for RyR in liver cells or that the site 
      of action of ryanodine in hepatocyte microsomes is distinct from that in other 
      cell types.
FAU - Lilly, L B
AU  - Lilly LB
AD  - Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA.
FAU - Gollan, J L
AU  - Gollan JL
LA  - eng
GR  - DK-36887/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Am J Physiol
JT  - The American journal of physiology
JID - 0370511
RN  - 0619F35CGV (Tetracaine)
RN  - 119340-53-3 (Cyclic ADP-Ribose)
RN  - 15662-33-6 (Ryanodine)
RN  - 20762-30-5 (Adenosine Diphosphate Ribose)
RN  - 3G6A5W338E (Caffeine)
RN  - 56092-81-0 (Ionomycin)
RN  - 85166-31-0 (Inositol 1,4,5-Trisphosphate)
RN  - 86-01-1 (Guanosine Triphosphate)
RN  - 8L70Q75FXE (Adenosine Triphosphate)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Adenosine Diphosphate Ribose/analogs & derivatives/pharmacology
MH  - Adenosine Triphosphate/metabolism
MH  - Animals
MH  - Caffeine/pharmacology
MH  - Calcium/*metabolism
MH  - Cell Membrane Permeability
MH  - Cells, Cultured
MH  - Cyclic ADP-Ribose
MH  - Guanosine Triphosphate/pharmacology
MH  - Inositol 1,4,5-Trisphosphate/pharmacology
MH  - Ionomycin/pharmacology
MH  - Kinetics
MH  - Liver/drug effects/*metabolism
MH  - Male
MH  - Microsomes, Liver/drug effects/*metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Ryanodine/*pharmacology
MH  - Tetracaine/pharmacology
MH  - Time Factors
EDAT- 1995/06/01 00:00
MHDA- 1995/06/01 00:01
CRDT- 1995/06/01 00:00
PHST- 1995/06/01 00:00 [pubmed]
PHST- 1995/06/01 00:01 [medline]
PHST- 1995/06/01 00:00 [entrez]
AID - 10.1152/ajpgi.1995.268.6.G1017 [doi]
PST - ppublish
SO  - Am J Physiol. 1995 Jun;268(6 Pt 1):G1017-24. doi: 10.1152/ajpgi.1995.268.6.G1017.