Functional overlap of IP(3)- and cADP-ribose-sensitive calcium stores in guinea pig myenteric neurons.
In myenteric neurons two different receptor subtypes govern the intracellular Ca(2+) stores: the inositol 1,4,5-trisphosphate (IP(3)) receptor (IP(3)R) and the ryanodine receptor (RyR). Their degree of functional overlap was determined by examining Ca(2+) release in these cells through both superfusion techniques and intracellular microinjection. Microinjection of IP(3) (50 microM) and cADP-ribose (cADPr, 50 microM), specific ligands for the IP(3)R and RyR, respectively, demonstrated mobilization of intracellular Ca(2+) stores. Perfusion with cinnarizine (50 microM) or dantrolene (10 microM), antagonists of the IP(3)R and RyR, respectively, eliminated the Ca(2+) response to microinjected IP(3) and cADPr. Superfusion of the neurons with 100 microM ATP, an IP(3)-mediated Ca(2+)-mobilizing agonist, caused intracellular Ca(2+) increments, which were antagonized by cinnarizine, and the RyR antagonists dantrolene, procaine (5 mM), and ryanodine (1 microM). Caffeine (10 mM) was applied repetitively in Ca(2+)-free conditions to deplete RyR-sensitive stores; subsequent perfusion with ATP demonstrated a Ca(2+) response. Conversely, caffeine caused a Ca(2+) response after repetitive ATP exposures. The internal Ca(2+) stores of myenteric neurons are governed by two receptor subtypes, IP(3)R and RyR, which share partial functional overlap.
Turner
D J
DJ
Department of Surgery, University of Michigan Medical Center, Ann Arbor, Michigan 48109, USA.
Segura
B J
BJ
Cowles
R A
RA
Zhang
W
W
Mulholland
M W
MW
D000246:Adenosine Diphosphate Ribose / Q000031:analogs & derivatives / Q000378:metabolism*; D000255:Adenosine Triphosphate / Q000494:pharmacology; D000779:Anesthetics, Local / Q000494:pharmacology; D000818:Animals; D001692:Biological Transport / Q000187:drug effects / Q000502:physiology; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002936:Cinnarizine / Q000494:pharmacology; D036563:Cyclic ADP-Ribose; D003620:Dantrolene / Q000494:pharmacology; D006168:Guinea Pigs; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism*; D008845:Microinjections; D009125:Muscle Relaxants, Central / Q000494:pharmacology; D009197:Myenteric Plexus / Q000166:cytology*; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D011343:Procaine / Q000494:pharmacology; D012433:Ryanodine / Q000494:pharmacology
D000779:Anesthetics, Local; D002121:Calcium Channel Blockers; D009125:Muscle Relaxants, Central; D010726:Phosphodiesterase Inhibitors; D036563:Cyclic ADP-Ribose; D012433:Ryanodine; D000246:Adenosine Diphosphate Ribose; D002936:Cinnarizine; D002110:Caffeine; D011343:Procaine; D015544:Inositol 1,4,5-Trisphosphate; D000255:Adenosine Triphosphate; D003620:Dantrolene; D002118:Calcium