Cellular mechanisms underlying adenosine actions on calcium
currents and cholinergic transmission in the enteric nervous
system.
Peres, Carlos Barajas-L[acute]opez Andrea L., & Rosa Espinosa-Luna.
Intestinal Disease Research Program, Department of Biomedical
Sciences, McMaster University, Hamilton, Ontario L8N 3Z5, Canada
APStracts 3:0053C, 1996.
Whole-cell recordings were used to investigate the effects of
adenosine and several of its analogs on voltage-activated calcium
currents (VACC) of myenteric and submucosal neurons.
Electrophysiological and pharmacological properties of the soma VACC
recorded in myenteric neurons indicate that they are carried through
N-type calcium channels, similar to those of the submucosal neurons
and to those of the calcium conductance that mediates ACh release at
the submucosal ganglia. Adenosinergic compounds inhibited, in a
concentration-response and in a voltage-dependent manner, VACC in
neurons from both enteric plexuses. The pharmacological profile of
the receptors that mediate this effect was similar to that of the
receptors involved in presynaptic inhibition in enteric neurons and
likely of the A1-subtype. The effects of 2-chloroadenosine (CADO) on
VACC were prevented by pretreatment with pertussis toxin (PT), became
irreversible with GTP-[gamma]-S (inside the pipette) and were
abolished with N-ethylmaleimide (NEM; known to uncouple receptors
from G-protein complexes). Intracellular recordings were used to
further evaluate presynaptic effects of adenosine at the submucosal
plexus. Adenosinergic compounds reduced the amplitude of fast
excitatory postsynaptic potentials (EPSPs) by acting at nerve
terminals. This effect was insensitive to PT and staurosporine (a
protein kinase inhibitor) but was abolished by NEM. CADO effects on
EPSPs were not reversed by increasing the extracellular calcium
concentration. In conclusion, activation of A1-adenosine receptors
inhibits VACC via PT-sensitive G-proteins in myenteric and submucosal
neurons. Reduction of cholinergic transmission also involves A1
-adenosine receptors and appears to involve the activation of PT
-insensitive G-proteins.
Received 20 July 1995; accepted in final form 31 January 1996.
APS Manuscript Number C443-5.
Article publication pending Am. J. Physiol. (Cell Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 14 February 96