In vivo stimulation of phosphoinositide metabolism in the brainstem of rats following osmotic stress.
We have investigated the effects of osmotic stress on the activity of inositol phospholipid turnover in the central nervous system of rats. Intracerebroventricular injection of [3H]myo-inositol was used for metabolic labelling of brain phosphoinositides in vivo. The levels of radiolabelled inositol lipids increased in a time-dependent manner in several areas of the brain, reaching a maximum 24 h after the injection. Treatment with LiCl 20 h after the administration of tritiated myo-inositol did not modify the levels of inositol lipids, but resulted in a dose-dependent accumulation of inositol phosphates. In rats treated with 10 mEq/kg LiCl, intraperitoneal injections of hypertonic saline (1.50 M NaCl) resulted in the stimulation of phosphoinositide turnover in the brainstem, but not in any of the other regions of the brain studied. This response was not prevented by unilateral cervical vagotomy, but was significantly lower in vasopressin-deficient Brattleboro rats. Brain phosphoinositide metabolism was not stimulated by acute blood volume depletion. We conclude that osmotic stress, but not acute hypovolemia, results in vasopressin-dependent activation of brainstem neurons by stimulating inositol phospholipid metabolism. In addition, metabolic labelling in vivo followed by treatment with LiCl provides a useful approach for assessing the physiological significance of the activation of polyphosphoinositide metabolism in the central nervous system in vivo. Our study provides evidence for a functional role of this second messenger system in the brainstem.
Moratalla
R
R
Medical Unit, Charing Cross and Westminster Medical School, Westminster Hospital, London, U.K.
Vallejo
M
M
Lightman
S L
SL
D000818:Animals; D001933:Brain Stem / Q000378:metabolism*; D008297:Male; D008563:Membrane Lipids / Q000378:metabolism; D010716:Phosphatidylinositols / Q000378:metabolism*; D051381:Rats; D011910:Rats, Brattleboro; D011919:Rats, Inbred Strains; D012462:Saline Solution, Hypertonic / Q000494:pharmacology*; D012965:Sodium Chloride / Q000494:pharmacology*; D014630:Vagus Nerve / Q000502:physiology; D014667:Vasopressins / Q000378:metabolism*
D008563:Membrane Lipids; D010716:Phosphatidylinositols; D012462:Saline Solution, Hypertonic; D014667:Vasopressins; D012965:Sodium Chloride