B. Driessen et al., FAILURE OF TYRAMINE TO RELEASE NEURONAL ATP AS A COTRANSMITTER OF NORADRENALINE IN THE GUINEA-PIG VAS-DEFERENS, Naunyn-Schmiedeberg's archives of pharmacology, 353(2), 1996, pp. 175-183
Contractions, release of noradrenaline and release of ATP elicited by
the indirectly acting sympathomimetic amine tyramine and responses eli
cited by exogenous noradrenaline were studied in the isolated vas defe
rens of the guinea pig. Release of noradrenaline was assessed as overf
low of tritium after preincubation with [H-3]-noradrenaline. ATP was m
easured by means of the luciferin-luciferase technique. In tissues pre
treated with pargyline 1 mM, tyramine 300 mu M, when added to the supe
rfusion medium for 2 min, elicited contraction and an overflow of trit
ium (mainly [H-3]-noradrenaline) and ATP. Contraction and ATP overflow
responses were prevented and tritium overflow was greatly reduced by
desipramine 10 mu M. Prazosin 0.3 CIM abolished contractions and evoke
d ATP overflow without changing tritium overflow. Blockade of postjunc
tional P-2,-purinoceptors by suramin 300 mu M caused a marked decrease
of tyramine-evoked contractions and a slight reduction of tritium ove
rflow whereas evoked ATP overflow was markedly increased. The effect o
n contraction was not shared by two other P,(2)-purinoceptor antagonis
ts, namely pyridoxalphosphate-6-azophenyl-2',4'-disulfonic acid (PPADS
) 32 mu M and diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS) 32
mu M: PPADS increased contractions about fourfold, whilst DIDS had no
effect at all. When the vas deferens was superfused for 24 min with me
dium containing tyramine 300 CIM, evoked contractions and tritium over
flow continued throughout whereas ATP overflow faded rapidly to basal
values. In the presence of prazosin 0.3 mu M, tyramine 300 mu M again
failed to elicit contractions as well as an overflow of ATP. Applicati
on of noradrenaline 10 mu M instead of tyramine also resulted in prolo
nged contraction and an overflow of ATP that declined rapidly. It is c
oncluded that all ATP released by tyramine is non-neuronal in origin,
secondary to the activation of postjunctional alpha(1)-adrenoceptors b
y released noradrenaline. The non-neural ATP does not seem to play a f
unctional role in smooth muscle contraction and derives from a postjun
ctional source which is subject to a rapid depletion upon sustained al
pha(1)-adrenoceptor activation.