title: Oxytocin-induced elevation of ADP-ribosyl cyclase activity, cyclic ADP-ribose or Ca(2+) concentrations is involved in autoregulation of oxytocin secretion in the hypothalamus and posterior pituitary in male mice.
abstract: Locally released oxytocin (OT) activates OT receptors (2.1:OXY:1:OT:) in neighboring neurons in the hypothalamus and their terminals in the posterior pituitary, resulting in further OT release, best known in autoregulation occurring during labor or milk ejection in reproductive females. OT also plays a critical role in social behavior of non-reproductive females and even in males in mammals from rodents to humans. Social behavior is disrupted when elevation of free intracellular Ca(2+) concentration ([Ca(2+)](i)) and OT secretion are reduced in male and female CD38 knockout mice. Therefore, it is interesting to investigate whether ADP-ribosyl cyclase-dependent signaling is involved in OT-induced OT release for social recognition in males, independent from female reproduction, and to determine its molecular mechanism. Here, we report that ADP-ribosyl cyclase activity was increased by OT in crude membrane preparations of the hypothalamus and posterior pituitary in male mice, and that OT elicited an increase in [Ca(2+)](i) in the isolated terminals over a period of 5 min. The increases in cyclase and [Ca(2+)](i) were partially inhibited by nonspecific protein kinase inhibitors and a protein kinase C specific inhibitor, calphostin C. Subsequently, OT-induced OT release was also inhibited by calphostin C to levels inhibited by vasotocin, an OT receptor antagonist, and 8-bromo-cADP-ribose. These results demonstrate that OT receptors are functionally coupled to membrane-bound ADP-ribosyl cyclase and/or CD38 and suggest that cADPR-mediated intracellular calcium signaling is involved in autoregulation of OT release, which is sensitive to protein kinase C, in the hypothalamus and neurohypophysis in male mice.
authors.affiliation: Kanazawa University 21st Century Center of Excellence Program on Innovative Brain Science on Development, Learning and Memory, Kanazawa 920-8640, Japan. ol.lopatina@gmail.com
authors.forename: Olga
authors.initials: O
authors.lastname: Lopatina
authors.forename: Hong-Xiang
authors.initials: HX
authors.lastname: Liu
authors.forename: Sarwat
authors.initials: S
authors.lastname: Amina
authors.forename: Minako
authors.initials: M
authors.lastname: Hashii
authors.forename: Haruhiro
authors.initials: H
authors.lastname: Higashida
mesh_terms: D036541:ADP-ribosyl Cyclase / Q000378:metabolism*; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D036563:Cyclic ADP-Ribose / Q000378:metabolism*; D007031:Hypothalamus / Q000166:cytology / Q000378:metabolism*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D010121:Oxytocin / Q000378:metabolism / Q000494:pharmacology; D010904:Pituitary Gland, Posterior / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D017729:Presynaptic Terminals / Q000378:metabolism; D013997:Time Factors
chemical_list: D036563:Cyclic ADP-Ribose; D010121:Oxytocin; D036541:ADP-ribosyl Cyclase; D002118:Calcium