Histamine H₁ and H₂ Receptor Activation Stimulates ACTH and β-Endorphin Secretion by Increasing Corticotropin-Releasing Hormone in the Hypophyseal Portal Blood

Abstract

Histamine (HA) stimulates the release of adrenocorticotropic hormone (ACTH) and β-endorphin (β-END) via activation of central postsynaptic H₁ or H₂ receptors. The effect of HA is indirect and may involve the hypothalamic regulating factors corticotropin-releasing hormone (CRH), arginine vasopressin, or oxytocin (OT). We studied the effect of specific HA H₁ or H₂ receptor agonists on the concentration of CRH and OT in hypophyseal portal blood in urethane-anesthetized male rats. In addition we investigated the effect of the agonists on ACTH and β-END immunoreactivity in peripheral plasma in conscious male rats pretreated with antiserum to CRH. Intracerebroventricular administration of the H₁ receptor agonist 2-thiazolylethylamine (2-TEA) or the H₂ receptor agonist 4-methylhistamine (4-MeHA) increased the CRH concentration in pituitary portal blood by 80-90% when compared to preinfusion levels (p < 0.05). Central infusion of saline had no effect. The level of OT in the pituitary portal blood was not affected by 2-TEA or 4-MeHA when compared to saline-treated rats. Intracerebroventricular infusion of 2-TEA or 4-MeHA increased the ACTH concentration in peripheral plasma 3- or 4-fold, respectively (p < 0.01). Pretreatment with a specific CRH antiserum (abCRH) inhibited the responses by 50 and 70%, respectively (p < 0.01). Intracerebroventricular administration of 2-TEA or 4-MeHA increased the β-END immunoreactivity in peripheral plasma 3- or 2-fold, respectively (p < 0.01). These effects were inhibited by 80-90%, when rats were pretreated with abCRH (p < 0.01). We conclude that the ACTH and β-END responses to activation of central histaminergic H₁ or H₂ receptors are mediated at least in part by hypothalamic CRH, whereas OT does not appear to be involved.

Effect of Selective Blockade of Catecholaminergic Alpha and Beta Receptors on Histamine-Induced Release of Corticotropin and Prolactin

“…These results indicate that the effect of HA on ACTH secretion is not mediated via catecholaminergic neurons or modulated by a concomitant presence of activated adrenergic receptors. The results resemble our previous finding that the serotonergic system does not participate in the mediation of the HA-induced ACTH release [14]and strengthens the hypothesis that HA affects ACTH secretion primarily via a direct activation of arginine vasopressin and in particular corticotropin-releasing hormone neurons in the parvocellular parts of the paraventricular nucleus [8, 9, 11, 19]. Whereas HA-induced stimulation of the HPA axis seems to be independent of serotonergic or adrenergic receptor activation [14], present study], we have previously found that HA interact with prostaglandins [13].…”

“…The ACTH antiserum (generously provided by the National Pituitary Agency, National Institute of Health) does not cross-react with β-endorphin or β-LPH and has less than 0.4% cross-reactivity with α- and β-melanocyte stimulating hormone. Synthetic human ACTH [1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39](generously provided by the National Pituitary Agency, National Institute of Health) served as reference preparation and iodination. The least detectable quantity of ACTH was 1 pmol/l plasma, and the intra- and interassay coefficients of variation were 4 and 5%.…”

“…It has been shown that HA stimulates ACTH secretion via corticotropin-releasing hormone, which originates in neurons of the paraventricular nucleus and via arginine vasopressin originating in neurons of the paraventricular nucleus and supraoptic nucleus [8, 9, 10, 11, 12]. In addition, we have recently found that HA interacts with prostaglandins but not with serotonin (5-HT) in the regulation of the hypothalamic-pituitary-adrenal (HPA) axis [13, 14].…”

Stress-Induced Release of Anterior Pituitary Hormones: Effect of H₃ Receptor-Mediated Inhibition of Histaminergic Activity or Posterior Hypothalamic Lesion

“…For the following reasons it is possible that one of the routes by which stress increases ACTH and β-END release is caused by excitation of histaminergic neurons in the posterior hypothalamus, which in turn activates CRH neurons in the PVN: histaminergic nerve fibers project from the tuberomammillary nuclei to the PVN [25, 26]; HA increases CRH synthesis and release in the PVN [62, 63]; antiserum to CRH inhibit the HA-induced release of ACTH and β-END [64], and CRH as well as HA mediate the stress-induced release of ACTH and β-END [8, 9, 10, 11, 18]. CRH released to the portal circulation then stimulates the secretion of the POMC-derived peptides.…”

Synthesis, F-18 radiolabeling, and microPET evaluation of 3-(2,4-dichlorophenyl)-N-alkyl-N-fluoroalkyl-2,5-dimethylpyrazolo[1,5-a]pyrimidin-7-amines as ligands of the corticotropin-releasing factor type-1 (CRF1) receptor

“…Activation of mast cells results in the release of histamine and other chemical messengers, 111 and histamine has been shown to increase levels of CRF in rats. 144, 145 This effect could be further enhanced by histamine receptor agonists or blocked by histamine receptor antagonists or anti-CRF. 144, 146, 147 In dog brain, mast cell degranulation results in an increase in histamine release and a subsequent increase in plasma cortisol and ACTH.…”