Central metabolic and pituitary-adrenocortical stimulatory action of histamine and clonidine.
This review presents our new findings regarding the centrally-induced effects of histamine and clonidine. We have found for the first time that histamine administered intracerebroventricularly (icv) induces a dose-related increase in serum free fatty acids (FFA) in conscious rats. Both H1 and H2 receptors participate in this stimulation. Histamine interacts with central alpha 1 and beta-adrenoceptors and with cholinergic muscarinic receptors when inducing hyperlipemic response in non-stressed rats. Clonidine given icv induces also hyperlipemia which, as shown by us, is elicited by a central alpha 2-adrenergic mechanism. In hypothermia caused in rats by clonidine not only already known central alpha-adrenergic but also an H2-histaminergic mechanism participates to an equal extent. We have found for the first time that in conscious rats both under normal and stress conditions not only central histamine H1- but also H2-receptors mediate the stimulation of the pituitary-adrenocortical response measured indirectly through corticosterone secretion. In our study evidence has for the first time been obtained that in non-stressed rats brain histaminergic mechanism interacts with alpha 1, alpha 2- and beta-adrenoceptors and with cholinergic muscarinic receptors when stimulating the pituitary-adrenocortical response. By contrast, in stressed animals central histamine H1- and H2-receptors interact with alpha 1- and alpha 2- but not beta-adrenergic and cholinergic muscarinic receptors when increasing the corticosterone response. We have also demonstrated that in contrast to a known inhibitory action on adrenocortical secretion in anesthetized dogs, clonidine given icv increases the corticosterone response in both non-stressed and stressed rats by stimulating alpha-adrenoceptors. In stressed animals this effect of clonidine is also mediated, to an equal extent, by H2-receptor mechanism. Our data strongly suggest that in some central effects clonidine affects both alpha 2 and H2 receptor mechanism. This challenges the view that clonidine is a selective alpha-adrenergic agonist.
D000818:Animals; D003000:Clonidine / Q000494:pharmacology*; D003345:Corticosterone / Q000502:physiology; D004285:Dogs; D006632:Histamine / Q000494:pharmacology* / Q000502:physiology; D006801:Humans; D006949:Hyperlipidemias / Q000139:chemically induced; D007276:Injections, Intraventricular; D009434:Neural Pathways / Q000502:physiology; D010275:Parasympathetic Nervous System / Q000187:drug effects; D010913:Pituitary-Adrenal System / Q000187:drug effects*; D051381:Rats; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects; D011969:Receptors, Histamine H1 / Q000502:physiology; D011970:Receptors, Histamine H2 / Q000502:physiology; D013315:Stress, Psychological / Q000503:physiopathology; D013564:Sympathetic Nervous System / Q000187:drug effects
D011942:Receptors, Adrenergic, alpha; D011969:Receptors, Histamine H1; D011970:Receptors, Histamine H2; D006632:Histamine; D003000:Clonidine; D003345:Corticosterone