Inhibition of small conductance K+-channels attenuated melatonin-induced relaxation of serotonin-contracted rat gastric fundus

The aim of this study was to investigate the effects of melatonin on rat ga stric fundus smooth muscle. Melatonin (10(-4) to10(-3) M) had no effect on the basal tone of gastric smooth muscle. After precontraction with carbacho l (10(-6) M) or serotonin (10(-7) M), melatonin caused a concentration depe ndent inhibitory action. The half maximal effect on serotonin-induced contr action was found with 1.12 beta 0.86 x 10(-5) M of melatonin. Increasing co ncentrations of melatonin (10(-5) to 10(-3) M) resulted in a right shift of the serotonin concentration response curve (10(-10) to 10(-5) M). This inh ibitory effect of melatonin was partially blocked in the presence of apamin (10(-10) to 10(-7) M), a specific blocker of the small conductance calcium -dependent potassium channel, but not in the presence of other potassium ch annel blockers like charybdotoxin (10(-8) M), glibenclamide (10(-5) M), or tetraethylammonium (ODQ, 10(-4) M). The inhibitory effect was not changed i n the presence of the neuronal blocker tetrodotoxin (10(-6) M), the selecti ve P-2-receptor antagonist pyridoxalphosphate-6-azophenyl-2',4'-disulphonic acid (3 x 10(-5) M), the nitric-oxide synthase inhibitor N-nitro-L-arginin e (3 x 10(-4) M), or the guanylate cyclase inhibitor 1H-[1,2,4]oxadiazolo[4 ,3-a]-quinoxalin-1-one (10(-4) M), suggesting that neither the purinergic, nitrergic, nor guanylate cyclase pathways were involved. We further investi gated inhibitory responses to electrical field stimulation (EFS) at differe nt frequencies under non-adrenergic, non-cholinergic (NANC) conditions on a serotonin-induced contraction in the presence of melatonin (10(-5) to 10(- 4) M). Melatonin significantly reduced these inhibitory NANC responses in h igher (8-32 Hz), but not lower (05-4 Hz), frequencies (16 Hz without melato nin, 103 +/- 6.3%; melatonin 10(-5) M, 80.4 +/- 7.5%; melatonin 10(-4) M, 3 9.1 +/- 17.1%). Melatonin had no effect on contractile responses induced by EFS under basal tone. These results demonstrate that the inhibitory effect of melatonin in rat gastric fundus smooth muscle is apamin sensitive, but is not affected by other potassium channel blockers. This suggests that mel atonin may be another transmitter candidate for the apamin sensitive respon ses within the gastrointestinal tract.