Ta. Hardy et Ja. Brock, Effects of agents that modulate intracellular cAMP levels on excitatory junction potentials recorded in the guinea-pig vas deferens in vitro, N-S ARCH PH, 362(6), 2000, pp. 559-567
This study used intracellular recording of excitatory junction potentials (
EJPs) and focal extracellular recording of excitatory junction currents (EJ
Cs) to investigate the effects of agents that modulate intracellular cAMP l
evels on sympathetic neuroeffector transmission in the guinea-pig vas defer
ens. In this tissue, postjunctional electrical activity is produced by neur
ally released ATP.
The adenylate cyclase activator, forskolin (0.5-5 muM) increased the amplit
ude of all EJPs evoked by trains of 20 stimuli at 1 Hz. Forskolin (5 muM) a
lso increased the probability of recording EJCs without changing the amplit
ude distributions of spontaneous EJP and EJCs, indicating that this agent d
oes not change the postjunctional sensitivity to spontaneously released qua
nta of ATP. EJP amplitudes were also increased by 8-bromo-cyclic AMP (10 mu
M), 8-bromo-cyclic GMP (10 muM), the phosphodiesterase inhibitor, 3-isobuty
l-1-methylxanthine (100 and 1000 muM) and the beta -adrenoceptor agonist, i
soprenaline (1 muM). The selective protein kinase A inhibitors, H-89 (10 mu
M) and the Rp isomer of adenosine-3',5'-cyclic monophosphorothioate (Rp-cAM
PS, 100 muM), and the broad spectrum protein kinase inhibitors, [1-(5-isoqu
inolinesulphonyl)-3-methylpiperazine-diHCl (H-7, 100 muM) and staurosporine
(1 muM), did not block the facilitatory effects of forskolin on EJP amplit
ude. In addition, the effects of forskolin were not blocked by the cyclic n
ucleotide-gated ion channel blocker, spermine (50 muM).
These results suggest that elevating intracellular cAMP levels increases AT
P release in the guinea-pig vas deferens by a mechanism which does not invo
lve activation of protein kinases A or G.