Dehydration-induced release of vasopressin involves activation of hypothalamic histaminergic neurons.
The hypothalamic neurotransmitter histamine (HA) induces arginine vasopressin (AVP) release when administered centrally. We studied and characterized this effect of HA with respect to receptor involvement. In addition, we studied the possible role of hypothalamic histaminergic neurons in the mediation of a physiological stimulus (dehydration) for AVP secretion. Intracerebroventricular administration of HA, the H1-receptor agonists 2(3-bromophenyl)HA and 2-thiazolylethylamine, or the H2-receptor agonists amthamine or 4-methyl-HA stimulated AVP secretion. The stimulatory action of HA on AVP was inhibited by pretreatment with the H1-receptor antagonist mepyramine or the H2-receptor antagonist cimetidine. Twenty-four hours of dehydration elevated the plasma osmolality from 298 +/- 3 to 310 +/- 3 mmol/liter and increased the plasma AVP concentration 4-fold. The hypothalamic content of HA and its metabolite tele-methyl-HA was elevated in response to dehydration, indicating an increased synthesis and release of hypothalamic HA. Dehydration-induced AVP secretion was lowered when neuronal HA synthesis was inhibited by the administration of (S) alpha-fluoromethylhistidine or when the animals were pretreated with the H3-receptor agonist R(alpha)methylhistamine, which inhibits the release and synthesis of HA, the H1-receptor antagonists mepyramine and cetirizine, or the H2-receptor antagonists cimetidine and ranitidine. We conclude that HA, via activation of both H1- and H2-receptors, stimulates AVP release and that HA is a physiological regulator of AVP secretion.
Department of Medical Physiology, Panum Institute University of Copenhagen, Denmark.
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Kjaer
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Knigge
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Rouleau
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Garbarg
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Warberg
D000818:Animals; D001127:Arginine Vasopressin / Q000378:metabolism*; D001769:Blood; D002927:Cimetidine / Q000494:pharmacology; D003681:Dehydration / Q000503:physiopathology*; D006632:Histamine / Q000008:administration & dosage / Q000494:pharmacology / Q000502:physiology*; D007031:Hypothalamus / Q000503:physiopathology*; D008297:Male; D008761:Methylhistamines / Q000494:pharmacology; D008762:Methylhistidines / Q000494:pharmacology; D009474:Neurons / Q000502:physiology*; D009994:Osmolar Concentration; D011738:Pyrilamine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011969:Receptors, Histamine H1 / Q000187:drug effects / Q000502:physiology; D011970:Receptors, Histamine H2 / Q000187:drug effects / Q000502:physiology
D008761:Methylhistamines; D008762:Methylhistidines; D011969:Receptors, Histamine H1; D011970:Receptors, Histamine H2; D001127:Arginine Vasopressin; C069357:alpha-methylhistamine; C028309:alpha-fluoromethylhistidine; D002927:Cimetidine; D006632:Histamine; D011738:Pyrilamine