Presynaptic mechanism of action induced by 5-HT in nerve terminals: possible involvement of ryanodine and IP3 sensitive 2+ stores.
Although modulation of transmitter release by serotonin (5-HT) at crayfish neuromuscular junctions has been known since 1965, the mechanisms of action have not been established in this classical synaptic preparation. We show that injections of adenophostin-A (an IP3 analog) in the nerve terminals greatly enhances synaptic transmission. Exposure to ryanodine (Ry) produces a biphasic response: at low concentration it is excitatory and high concentration it is inhibitory. Likewise, a low concentration (1 microM) of caffeine enhances synaptic transmission, whereas a high concentration (10 mM) has little effect on transmission. The varied responses and sensitivity to Ry and caffeine suggest a Ca(2+)-induced Ca(2+)-release mechanism and/or the presence of an IP3-receptor within the terminal. Thus, it is likely 5-HT's response is due to activation of intracellular pathways, which subsequently release Ca2+ from internal stores.
Dropic
Amanda J
AJ
Department of Biology, University of Kentucky, Lexington, KY 40506-0225, USA.
Brailoiu
Eugen
E
Cooper
Robin L
RL
D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D003400:Astacoidea / Q000502:physiology; D002110:Caffeine / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects* / Q000502:physiology; D053496:Inositol 1,4,5-Trisphosphate Receptors; D008564:Membrane Potentials / Q000187:drug effects; D009469:Neuromuscular Junction / Q000187:drug effects* / Q000502:physiology; D017729:Presynaptic Terminals / Q000187:drug effects* / Q000502:physiology; D018160:Receptors, Cytoplasmic and Nuclear / Q000187:drug effects* / Q000502:physiology; D012433:Ryanodine / Q000494:pharmacology*; D019837:Ryanodine Receptor Calcium Release Channel / Q000187:drug effects* / Q000502:physiology; D012701:Serotonin / Q000494:pharmacology*
D015220:Calcium Channels; D053496:Inositol 1,4,5-Trisphosphate Receptors; D018160:Receptors, Cytoplasmic and Nuclear; D019837:Ryanodine Receptor Calcium Release Channel; C085029:adenophostin A; D012433:Ryanodine; D012701:Serotonin; D002110:Caffeine; D000241:Adenosine