Effect of histamine on the secretion of pro-opiomelanocortin derived peptides in rats

Abstract

In conscious male rats intracerebroventricular infusion of histamine increased the plasma concentrations of ACTH and \g=b\-endorphinimmunoreactivity 2.5-fold (P < 0.01). Gel filtration of plasma revealed two peaks of \g=b\-endorphinimmunoreactivity corresponding to \g=b\-endorphin and \g=b\-lipotropin. The two fractions increased almost equally in histamine-stimulated animals, whereas most of the circulating \g=b\-endorphin immunoreactivity in control animals corresponded to \g=b\-endorphin. Central infusion of the H1\ x=r eq-\ receptor agonist 2-thiazolylethylamine and of the H2\ x=r eq-\ receptor agonists dimaprit or 4-methylhistamine increased the plasma ACTH and \g=b\-endorphin immunoreactivity concentrations 2-and 3-fold, respectively (P < 0.01). Infused intracerebroventricularly, the H2\ x=r eq-\ receptor antagonists cimetidine or ranitidine prevented the histamine-induced increase in plasma ACTH and \g=b\-endorphinimmunoreactivity (P < 0.01), whereas the H1-receptor antagonist mepyramine inhibited the peptide responses by 70% (P < 0.01). Infused intra-arterially cimetidine or ranitidine inhibited the histamine\x=req-\ induced increase in plasma ACTH by 80% (P < 0.01) and plasma \g=b\-endorphinimmunoreactivity by 45% (P < 0.05), whereas mepyramine or the other H1-receptor antagonist SKF-93944 inhibited the ACTH response by 50% (P < 0.05), but had no effect on the \g=b\-endorphinimmunoreactivity. The results indicate that histamine increases the release of the pro-opiomelanocortin derived peptides ACTH, \g=b\-lipotropin and \g=b\-endorphin from the anterior pituitary lobe, whereas an effect of histamine on the release of \g=b\-endorphin from the neurointermediate lobe is possible. The effect of histamine seems primarily mediated by H2-receptors, whereas H 1-receptors appear to play a minor role.

Neuronal histamine and expression of corticotropin-releasing hormone, vasopressin and oxytocin in the hypothalamus: relative importance of H1 and H2 receptors

“…This may indicate the existence of a basal H 2 -receptor-mediated histaminergic tone on CRH synthesis. However, this effect is not important for basal ACTH and b-endorphin secretion since CIM did not influence basal secretion of these hormones (23). Neither the H 1 -nor the H 2 -receptor antagonist inhibited the HA-induced increase in CRH mRNA.…”

“…The present data are therefore in accordance with our previous findings that H 1 -and H 2 -receptor activation by the same agonists, as used here and in similar doses, stimulated CRH release into the long pituitary portal vessels in anesthetized rats (16). It is therefore likely that the previously demonstrated stimulatory effect of H 1 -and H 2 -receptor agonists on ACTH and b-endorphin secretion (16,23) is mediated at least in part by activation of CRH neurons. In support of this hypothesis, the agonist-induced ACTH and b-endorphin secretion was inhibited by immunoneutralization of endogenous CRH (16).…”

“…This dose was previously shown to be able to stimulate neuropeptide mRNA levels (14). The doses of 2-TEA and 4-MeHA were chosen to be equipotent to the HA dose with respect to ACTH release (23).…”

Effect of blockade of postsynaptic H1 or H2 receptors or activation of presynaptic H3 receptors on catecholamine-induced stimulation of ACTH and prolactin secretion

“…The catecholaminergic compounds E and NE were administered in an equimolar dose of 5 mmol icv. The doses of MEP (350 nmol icv) and CIM (400 nmol icv) have previously been found to inhibit HA-induced hormone release (26,29) and the dose of IME (2 mg/ kg ip) has been found to inhibit stress-induced hormone release (30).…”

“…The blood samples were centrifuged at 4 ЊC and plasma was stored at ¹20 ЊC until analyzed for ACTH and PRL by specific radioimmunoassays (29,31). The hormone determinations were performed in unextracted plasma.…”