Post- and pre-synaptic action of isotocin in the upper esophageal sphincter muscle of the eel: its role in water drinking

Isotocin is a fish analogue of the mammalian hormone oxytocin. To elucidate sites of action of isotocin (IT) in the upper esophageal sphincter (UES) muscle, a key muscle in swallowing, IT was applied after treatment with tetrodotoxin (TTX). Even after blocking nerve activity with TTX, IT relaxes the UES muscle in a concentration-dependent manner, suggesting that IT receptor(s) is present on the muscle cells. Similar relaxation was also obtained by application of 3-isobutyl-1-methylxanthine (IBMX), forskolin (FSK) and 8-bromo-adenosine, 3′,5′-cyclic monophosphate (8BrcAMP) after pretreatment with TTX, suggesting that the relaxing effect (postsynaptic action) of IT may be mediated by cAMP. In contrast to such relaxing effect, IT enhanced the UES contraction induced by repetitive electrical field stimulation (EFS). Such enhancement was blocked by an IT receptor antagonist, suggesting that this effect is also mediated by IT receptor(s). Similar enhancement was also induced by IBMX, FSK and 8BrcAMP, suggesting the enhancing effect is also mediated by cAMP. However, no enhancing effect of IT was observed when the muscle was stimulated by carbachol, or after treatment with curare or TTX, denying the postsynaptic modulatory action of IT and suggesting presynaptic action for IT, i.e., accelerating acetylcholine release. Summarizing these results, role of IT in precisely regulating the drinking rate in the seawater eel is discussed.