Effect of compound 48/80 on mast cells and histamine levels in rat brain and on corticosterone secretion.
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Animals↗
Biomedical subjects
J Borycz
Publications and source records attributed to J Borycz.
Mediation by nitric oxide of the carbachol-induced corticosterone secretion in rats.
Nitric oxide synthase, an enzyme responsible for nitric oxide (NO) formation has been found in the hypothalamic paraventricular nucleus and median eminence, structures closely associated with regulation of the pituitary activity, and the pituitary gland itself. Nitric oxide modulates the stimulated release of CRH from the rat hypothalamus in vitro, which suggests its role in regulating the secretion of ACTH from the pituitary corticotrops and of corticosterone from the adrenal cortex. The purpose of the present study was to elucidate the yet unknown role of endogenous NO in the HPA response to central cholinergic stimulation in conscious rats. Neither L-arginine an NO precursor, nor the NO synthase blockers N omega-nitro-L-arginine methyl ester (L-NAME) and N omega-nitro-L-arginine (L-NNA) caused any consistent changes in the basal serum corticosterone levels. L-arginine, given in higher doses (120-150 mg/kg ip) 15 min prior to icv carbachol (2 micrograms), markedly diminished the carbachol-induced rise in corticosterone secretion. Systemic pretreatment with the nitric oxide synthase inhibitor L-NAME (5 mg/kg) significantly raised the carbachol-elicited corticosterone response, while addition of L-arginine completely blocked the effect of L-NAME. A similar increase in the carbachol-induced corticosterone response was produced by icv pretreatment with L-NAME (2 micrograms), indicating a central site of the NO interaction with cholinergic stimulation of the HPA response. L-NAME is a weak inhibitor of neuronal NOS itself, and must first be de-estrified to N omega-nitro-L-arginine to potently inhibit this enzyme. Systemic (10 mg/kg) and icv (1 microgram) pretreatment with L-NNA enhanced more effectively the carbachol-induced rise in corticosterone secretion than did pretreatment with L-NAME by either route. These results are the first direct evidence that endogenous NO significantly inhibits the HPA response to central cholinergic, muscarinic receptor stimulation under in vivo conditions.
Animals↗
Effect of indomethacin on the pituitary-adrenocortical response to adrenergic stimulation.
The role of prostaglandins (PGs) in stimulation of the hypothalamic-pituitary-adrenal (HPA) axis by adrenergic agonists and catecholamines was investigated in nonanesthetized rats. The cyclooxygenase and PGs synthesis inhibitor indomethacin was given systemically or intracerebroventricularly (icv) 15 min prior to phenylephrine (30 micrograms), clonidine (10 micrograms), and isoproterenol (20 micrograms), an alpha 1-, alpha 2-, and beta-adrenergic receptor agonists, respectively, or noradrenaline (10 micrograms) and adrenaline (10 micrograms). Indomethacin given ip (2 mg/kg) or icv (10 micrograms) almost abolished the increase in corticosterone secretion elicited by phenylephrine, considerably reduced the response to clonidine but did not markedly affect the response to isoproterenol. Pretreatment with indomethacin by either route strongly suppressed the corticosterone response to noradrenaline, but did not substantially affect the hormonal response to adrenaline. The above data indicate that prostaglandins considerably mediate the HPA axis response to central stimulation of alpha 1- and alpha 2-, but not beta-adrenergic receptors. They also point to significant involvement of prostaglandins in the noradrenaline-, but not adrenaline-induced HPA axis predominantly via alpha 1-and alpha 2-adrenergic receptors, whereas adrenaline exerts stimulation manly via beta-adrenergic receptors.
Adrenal Cortex↗
Effect of indomethacin on the CRH- and VP-induced pituitary-adrenocortical response during social stress.
The role of prostaglandins (PGs) on the corticotropin-releasing hormone (CRH)- and vasopressin (AVP)-induced pituitary-adrenocortical response under basal and social stress circumstances was investigated. Crowding stress applied for 3 days did not diminish the CRH-elicited corticosterone response, but it considerably reduced such a response to AVP. In control rats systemic or icv pretreatment with indomethacin, an inhibitor of PGs synthesis, did not affect the corticosterone response to ip or icv CRH administered 15 min later. By contrast, ip or icv pretreatment with indomethacin considerably reduced the corticosterone response to AVP given by either route in control rats. Similarly, ip pretreatment with indomethacin further reduced the corticosterone response to AVP already diminished by crowding stress. These results indicate that hypothalamic and anterior pituitary PGs are not involved in the CRH-elicited pituitary-adrenocortical response, but they significantly mediate this response to AVP under both basal and social stress circumstances.
Adrenal Cortex↗
The role of prostaglandins and the hypothalamic and hippocampal histamine in the clonidine-induced pituitary-adrenocortical response.
Involvement of prostaglandins (PGs) and histamine in the hypothalamus and hippocampus in the clonidine-induced pituitary-adrenocortical response was investigated in conscious rats. The hypothalamic-pituitary adrenocortical (HPA) activity was assessed indirectly by measuring corticosterone secretion. Clonidine, an alpha 2-adrenergic agonist, given intracerebroventricularly (10 micrograms icv), considerably increased the serum corticosterone and hypothalamic histamine levels and markedly elevated the hippocampal histamine levels. Systemic or icv pretreatment with indomethacin (2 mg/kg or 10 micrograms), an inhibitor of prostaglandin synthesis, significantly reduced the clonidine-induced corticosterone response and abolished the increase in the hypothalamic and hippocampal histamine levels elicited by clonidine. Indomethacin in the doses used did not substantially change the resting serum corticosterone or hypothalamic and hippocampal histamine levels. These results indicate that prostaglandins and hypothalamic histamine are considerably involved in the HPA response to alpha 2-adrenergic receptor stimulation. They also suggest involvement of prostaglandins and histamine of the hippocampus in the clonidine-induced HPA response.
Adrenergic alpha-Agonists↗
Central histaminergic mechanisms mediate the vasopressin-induced pituitary adrenocortical stimulation.
Involvement of histamine receptors and hypothalamic and hippocampal histamine in stimulation of the hypothalamic-pituitary-adrenal (HPA) axis by vasopressin (AVP) was investigated in conscious rats. The HPA activity was assessed by measuring serum corticosterone levels. One hour after administration AVP, (5 micrograms/kg) given i.p. significantly raised the serum corticosterone and hippocampal histamine levels, while the hypothalamic histamine content was not affected. Pretreatment with the inhibitor of the brain histamine synthesis alpha-fluoromethylhistidine (alpha-FMH) (50 mg/kg i.p.) considerably reduced both the AVP-elicited serum corticosterone response and the hypothalamic and hippocampal histamine levels. The histamine H1- and H2-receptor-antagonists mepyramine (0.01 mg/kg) and ranitidine (0.1 mg/kg), given ip 15 min prior to AVP, significantly impaired the AVP-induced rise in the serum corticosterone level and totally abolished the AVP-elicited increase in the histamine content in the hippocampus; moreover mepyramine significantly lowered this content in hypothalamus. Pretreatment with the histamine H3-receptor antagonist thioperamide (5 mg/kg i.p.) also significantly decreased the AVP-elicited corticosterone response, but did not alter the histamine content in either brain structure examined. These results indicate that central histamine H1-, H20 and H3-receptors significantly mediate the stimulatory action of AVP on the pituitary-adrenocortical axis. Hippocampal histamine may be involved in mediation of the AVP-induced effect via H1- and H2-receptors. The inhibitory effect of thioperamide seems to be located directly at non H3-intracellular sites of the pituitary-adrenocortical axis.
Adrenocorticotropic Hormone↗
Crowding stress impairs the pituitary-adrenocortical responsiveness to the vasopressin but not corticotropin-releasing hormone stimulation.
To evaluate the effect of social crowding stress on the CRH and vasopressin-induced hypothalamic-pituitary-adrenocortical (HPA) response, both those neuropeptides were administered intracerebroventricularly and intraperitoneally to rats crowded for 3 days. Crowding stress did not affect the corticosterone response to CRH given by either route (1 micrograms i.c.v. or 2 micrograms/kg i.p.) but totally abolished or considerably diminished the response to vasopressin given i.p. (5 micrograms/kg) or i.c.v. (5 micrograms), respectively. Social crowding stress considerably impairs central vasopressin but does not change the CRH-system involved in the HPA stimulation.
Adrenocorticotropic Hormone↗
The corticosterone response to cholinergic and CRF receptor stimulation in rats exposed to social crowding stress.
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Animals↗
Degranulation and decrease in histamine levels of thalamic mast cells coincides with corticosterone secretion induced by compound 48/80.
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Animals↗
Involvement of central histaminergic mechanisms and prostaglandins in carbachol-induced corticosterone secretion.
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Animals↗
Adrenergic regulation of the hypothalamic-pituitary-adrenal axis under basal and social stress conditions.
The significance of adrenergic neurons and anterior pituitary and hypothalamic adrenergic receptors in stimulation of the hypothalamic-pituitary-adrenal (HPA) axis by corticotropin releasing hormone (CRH) and vasopressin (AVP) was investigated under basal conditions and after three-days crowding stress in conscious rats. In nonstressed rats the corticosterone response to phenylephrine, an alpha 1-adrenergic receptor agonist, was totally abolished or considerably reduced by prazosin, an alpha 1-receptor antagonist, when both those drugs were given ip or icv, respectively. The corticosterone response to ip isoproterenol, a beta-adrenergic agonist, was abolished by icv or ip pretreatment with propranolol, a beta-adrenergic receptor antagonist. These results indicate involvement of functional alpha 1-adrenoceptors in the hypothalamus and anterior pituitary corticotrops and pituitary beta-adrenoceptors in stimulation of the HPA axis. AVP given ip was almost as potent as CRH in stimulating corticosterone secretion. The stimulatory effect of AVP given ip or icv on corticosterone secretion was significantly diminished by propranolol, but not prazosin or yohimbine, indicating an involvement of beta-adrenergic receptors. The specific noradrenergic neurotoxin DSP-4, given ip 11 days before the experiment, considerably diminished the hypothalamic noradrenaline (NA) level but did not influence the resting and icv CRH- or AVP-stimulated corticosterone secretion. In nonstressed rats CRH further enhanced significantly the DSP-4-elicited fall in hypothalamic NA, whereas AVP almost totally prevented that decrease. In stressed rats CRH considerably antagonized the DSP-4-induced decrease in the hypothalamic NA level while AVP did not affect that decrease. The CRH- and AVP-elicited changes in hypothalamic NA were not correlated with changes in corticosterone secretion. Tree-day crowding stress did not affect the CRH-induced corticosterone secretion, whereas it considerably reduced the AVP-evoked corticosterone response. These results indicate that pituitary and hypothalamic adrenergic receptors are significantly involved in the AVP- and CRH-induced HPA axis stimulation, but the hypothalamic NA level, though modified by these peptides, does not significantly influence the HPA response.
Adrenal Glands↗
Effect of compound 48/80 on mast cells and biogenic amine levels in brain structures and on corticosterone secretion.
The effect of compound 48/80, given intracerebroventricularly, on mast cells (MC) and histamine, serotonin and noradrenaline levels in the hypothalamus, thalamus and hippocampus as well as on corticosterone secretion was investigated in rats. A relatively high amount of mast cells was found in the thalamus, a very low in the hypothalamus and almost none in the hippocampus. Compound 48/80 (1 and 5 micrograms) induced MC degranulation, a significant increase in corticosterone secretion and diminution of the thalamic histamine level. The drug also elicited small biphasic changes in histamine level in the hypothalamus and moderately increased serotonin turnover in the brain structures studied, but did not affect noradrenaline level in those structures. These results indicate that brain MC contain a significant amount of histamine, but not serotonin. Compound 48/80 releases histamine from MC, but does not markedly influence neuronal biogenic amines in the brain structures involved in regulation of the hypothalamic-pituitary-adrenal axis.
Animals↗
Effect of crowding on corticosterone responses to central adrenergic stimulation.
The social stress of crowding for 3, 7 and 14 days considerably reduced the increase in serum corticosterone elicited by intracerebroventricular administration of isoprenaline, a beta-adrenergic agonist, on the 3rd and 7th days of crowding. The corticosterone response to clonidine, an alpha 2-adrenergic agonist, was significantly diminished only after 3 days of crowding and this reduction was paralleled by a significant decrease in hypothalamic histamine content. The stimulatory effect of phenylephrine, an alpha 1-adrenergic agonist, was not significantly changed by crowding stress. Social crowding stress caused almost total and persistent reduction in the hypothalamic-pituitary-adrenocortical (HPA) responsiveness to noradrenaline which stimulates the HPA axis via both alpha- and beta-adrenergic receptors.
Animals↗
Effect of social isolation on corticosterone secretion elicited by histaminergic stimulation.
The effects of social stress of isolation for 3, 7, and 14 days on the responsiveness of the hypothalamic-pituitary-adrenocortical (HPA) axis to the stimulation of central histamine receptors and on the contents of hypothalamic biogenic amines were investigated. The corticosterone response to intraventricular administration of pyridylethylamine (PEA), a histamine H1-receptor agonist, was significantly higher in isolated than in control rats. The corticosterone response to dimaprit, a histamine H2-receptor agonist, tended to be slightly weaker in the stressed rather than in control rats. PEA significantly diminished the hypothalamic noradrenaline, dopamine and serotonin contents in both control and isolated rats. Dimaprit also decreased the brain NA, but not the DA concentrations in control and isolated rats. The changes in monoamines were not correlated with either the time, direction or magnitude of changes in corticosterone levels. These results suggest that hyperresponsiveness of the HPA system to the stimulation of central H1-histamine receptors during social isolation may depend on changes in the efficacy of H1 receptors but not on changes in the brain monoamine levels.
Animals↗
Pituitary-adrenocortical responsiveness to histaminergic stimulation during social stress of crowding in rats.
Social stress of crowding for 3, 7, 14 and 21 days drastically reduces the serum corticosterone response to intracerebroventricular administration of dimaprit, a histamine H2-receptor agonist, moderately diminishes the response to pyridylethylamine, an H1-receptor agonist, and does not change significantly the corticosterone response to histamine. These results suggest that social stress of crowding considerably desensitizes central histamine H2-receptors involved in stimulation of the hypothalamic-pituitary-adrenal axis.
Animals↗
Effect of compound 48/80 on the thalamic mast cells, serotonin level and corticosterone secretion in rats.
The effect of thalamic mast cells (MCs) degranulation and serotonin liberation by compound 48/80 on the hypothalamic-pituitary-adrenocortical (HPA) activity, measured indirectly through corticosterone secretion, was investigated in conscious rats. All drugs were given intracerebroventricularly (icv), the serotonin antagonists 15 min prior to compound 48/80. One hour after administration, compound 48/80 (1 and 5 micrograms) caused a significant increase in degranulated MC number in the thalamus, from control value of 20% up to 58%, and a considerable rise in the serum corticosterone level, but only minor diminution of the thalamic serotonin content. Pretreatment with methysergide, a serotonin receptor antagonist, only slightly dimished the compound 48/80-induced corticosterone response, while pretreatment with cyproheptadine, an antagonist of serotonin-histamine and cholinergic-receptors, significantly decreased the compound 48/80-elicited corticosterone response. These results show for the first time that thalamic mast cells contain a very small amount of serotonin, which may play only a minor role in increasing the HPA activity by compound 48/80. These findings also suggest that other mediators liberated from mast cells by compound 48/80 are responsible for the considerable increase in the HPA activity.
Animals↗
Effect of corticotropin releasing hormone on the pituitary-adrenocortical activity under basal and social stress conditions.
The effect of social crowding stress on the CRH-induced hypothalamic-pituitary-adrenocortical (HPA) responsiveness was assessed in rats crowded for 3 days, when the HPA response to neurotransmitter receptors stimulation was powerfully reduced. CRH given systemically dose-dependently increased the secretion of corticosterone. The increase was not affected by pretreatment with prazosin or propranolol, an alpha 1- or beta-adrenergic receptor antagonist, indicating the lack of involvement of adrenergic receptors in that stimulation. In the corticosterone response to CRH administered icv, a moderate involvement of hypothalamic alpha 1-adrenergic receptors and neuronal noradrenaline seems possible. The corticosterone responses to CRH given by either route to rats exposed to social crowding stress were identical with the responses of unstressed controls. Our results for the first have time shown that social crowding stress does not impair the HPA responsiveness to CRH stimulation.
Animals↗
Histaminergic components in carbachol-induced pituitary-adrenocortical activity.
The involvement of central histaminergic mechanisms in stimulation of the hypothalamic-pituitary-adrenal (HPA) axis by carbachol, a muscarinic cholinergic agonist, was investigated in conscious rats. The HPA activity was assessed indirectly, through corticosterone secretion. Carbachol given intracerebroventricularly elicited a dose-related increase in serum corticosterone levels. The corticosterone response to carbachol was totally abolished by systemic pretreatment 2h earlier with alpha-fluoro-methylhistidine (alpha-FMH), a specific inhibitor of brain histamine synthesis, which also significantly decreased histamine level in hypothalamus. Mepyramine, a histamine H1-receptor antagonist, moderately diminished the carbachol-induced corticosterone response and abolished the rise in hypothalamic histamine levels. Ranitidine a H2-receptor antagonist, considerably diminished the corticosterone response to carbachol but did not change the elevated hypothalamic histamine levels. Also atropine, a cholinergic antagonist, abolished the corticosterone response to carbachol, but did not significantly affect the carbachol-induced increase in hypothalamic histamine concentration. Ranitidine and atropine can directly block homologous hypothalamic receptors involved in CRF secretion. Partial inhibition of the carbachol-induced corticosterone secretion by mepyramine may be connected with prevention of the carbachol-induced increase in hypothalamic histamine content. These results suggest that hypothalamic histamine and histamine receptors are involved in the HPA stimulation by the muscarinic agonist carbachol.
Animals↗