Adenosine agonists reduce voltage-dependent calcium conductance of mouse sensory neurones in cell culture.
Adenosine and several of its analogues produced a concentration-dependent shortening of calcium-dependent action potential (c.a.p.) duration of mouse dorsal root ganglion (d.r.g.) neurones in dissociated cell culture. The following rank order of potency was obtained: N6-(L-phenylisopropyl)adenosine greater than N6-(D-phenylisopropyl)adenosine greater than N6-cyclohexyladenosine greater than 2-chloroadenosine much greater than 1-methylisoguanosine greater than adenosine. Effects of adenosine agonists on c.a.p. duration were blocked by methylxanthine adenosine antagonists. Adenosine monophosphate (AMP) and cyclic AMP shortened c.a.p.s in d.r.g. neurones, while ATP also depolarized cells. Voltage-clamp analysis revealed that the effect arose from reduction of a voltage-dependent calcium conductance. Adenosine agonists reduced depolarization-evoked inward currents but did not alter membrane conductance following blockade of calcium channels by cadmium. Additionally, adenosine reduced the instantaneous current-voltage slope (chord conductance) during step commands that produced maximal activation of voltage-dependent calcium conductance. If effects of adenosine on neuronal somata and synaptic terminals are similar, adenosine agonists may inhibit neurotransmitter release in the central nervous system by inhibiting a voltage-dependent calcium conductance. Since effects of adenosine agonists did not correspond with their relative potencies as modulators of adenylate cyclase activity or inhibitors of neurotransmitter release in peripheral tissues, a novel adenosine receptor may be involved in regulation of this conductance.
R L
RL
MacDonald
J H
JH
Skerritt
M A
MA
Werz
D000200:Action Potentials / Q000187:drug effects; D000227:Adenine Nucleotides / Q000494:pharmacology; D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology*; D000818:Animals; D002104:Cadmium / Q000494:pharmacology; D002118:Calcium / Q000502:physiology*; D002478:Cells, Cultured; D005727:Ganglia, Spinal / Q000166:cytology; D007473:Ion Channels / Q000187:drug effects; D051379:Mice; D009475:Neurons, Afferent / Q000502:physiology*; D010660:Phenylisopropyladenosine / Q000494:pharmacology
D000227:Adenine Nucleotides; D007473:Ion Channels; D002104:Cadmium; D010660:Phenylisopropyladenosine; D000241:Adenosine; D002118:Calcium