title: Aluminum fluoride reveals a phosphoinositide system within the suprachiasmatic region of rat hypothalamus.
abstract: The phosphoinositide (PI) transduction system has proven to be of major importance in several regions of mammalian brain. In this report, we examined in rats whether a PI system is present in the hypothalamic suprachiasmatic nuclei (SCN), the site of a biological clock that generate circadian rhythms. Autoradiographic localization of phorbol ester binding revealed moderate levels of protein kinase C, a component of the PI system, in the SCN. Hypothalamic explants containing SCN showed substantial incorporation of [3H]myoinositol into lipids. AlF4-, a non-specific activator of G proteins, produced a dose-dependent increase in inositol monophosphate (IP1) levels in the explants in calcium-free medium, with a maximum increase of 216% of control at 50 mM NaF. Medium containing 1.8 mM calcium stimulated a similar increase in IP1 levels, but the stimulatory effects of AlF4- and calcium were not additive, so that the effect of Al4- was obscured in medium containing calcium. AlF4- stimulated accumulation of IP1, as well as inositol bis-, and trisphosphate, over a 40-min time course in the presence and absence of lithium (10 mM LiCl). Lithium, a known inhibitor of phosphatases in the inositol phosphate recycling pathway, raised levels of all 3 inositol phosphates in SCN explants both at baseline (without A1F4-) and after 30 min AlF4- stimulation. The results show the existence of a lithium-sensitive PI system within the suprachiasmatic region of the rat hypothalamus.
authors.affiliation: Laboratory of Developmental Chronobiology, Children's Service, Massachusetts General Hospital, Boston 02114.
authors.forename: J J
authors.initials: JJ
authors.lastname: Nadakavukaren
authors.forename: D K
authors.initials: DK
authors.lastname: Welsh
authors.forename: S M
authors.initials: SM
authors.lastname: Reppert
mesh_terms: D000535:Aluminum / Q000494:pharmacology*; D017607:Aluminum Compounds; D000818:Animals; D002118:Calcium / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005459:Fluorides / Q000494:pharmacology*; D019204:GTP-Binding Proteins / Q000378:metabolism / Q000502:physiology*; D008274:Magnesium / Q000494:pharmacology; D008297:Male; D010716:Phosphatidylinositols / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D013493:Suprachiasmatic Nucleus / Q000187:drug effects / Q000378:metabolism*
chemical_list: D017607:Aluminum Compounds; D010716:Phosphatidylinositols; D000535:Aluminum; D019204:GTP-Binding Proteins; D008274:Magnesium; D005459:Fluorides; D002118:Calcium; C032311:aluminum fluoride