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J Borycz

Publications and source records attributed to J Borycz.

At least 19 recordsLinked to original sources
PubMed2000

The determination of histamine in the Drosophila head.

Histamine is a neurotransmitter at arthropod photoreceptors. Even though the fruit fly, Drosophila melanogaster, is a widely used model in neuroscience research, the histamine content of its nervous system has not so far been reported. We have developed a high performance liquid chromatography (HPLC) method with pre-column o-phtaldialdehyde-mercaptoethanol (OPA-ME) derivatization and electrochemical detection, to determine this amine in Drosophila. The histamine content of the fly's head averages about 2.0 ng per head. In heads of the mutant hdc(JK910), a presumed null for the gene encoding the enzyme that synthesizes histamine, histamine was not detected in measurable amounts. In heads of the mutant sine oculis, which lacks compound eyes, only 28% of this amine was found compared with wild type flies, so histamine is mainly present in the compound eye photoreceptors. Also observed in histamine-deficient mutants was a decrease in the peak which contains a substance having the same retention time as carcinine (beta-alanyl-histamine). Our method was not able to detect compounds previously reported as histamine metabolites in insects. In spite of this, the method we have developed enables the fast and accurate measurement of histamine in the heads of Drosophila, suitable for screening mutants.

Animals↗
PubMed2000

Stimulation of group II metabotropic glutamate receptors or inhibition of group I ones exerts anxiolytic-like effects in rats.

Using the conflict drinking Vogel test in rats as a model we examined the anxiolytic-like activity of (S)-4-carboxyphenylglycine (S-4CPG), an antagonist of group I metabotropic glutamate receptors (mGlu receptors), of (RS)-a-methylserine-O-phosphate-monophenyl ester (MSOPPE), an antagonist of group II mGlu receptors, and of (2S,1'S,2'S)-2-(carboxycyclopropyl)glycine (L-CCG-I), an agonist of group II mGlu receptors. The obtained results indicate that intrahippocampal administration of S-4CPG and L-CCG-I, but not MSOPPE to rats produces a dose-dependent anticonflict effect, which is unrelated to the reduced perception of the stimulus or to an increased thirst drive. The hippocampus may be one of the neuroanatomical sites of the anxiolytic-like effects of either agent.

Animals↗
PubMed1999

On the bioactive conformation of NAN-190 (1) and MP3022 (2), 5-HT(1A) receptor antagonists.

Structural modifications of 1, a postsynaptic 5-HT(1A) receptor antagonist, provided its flexible (8, 12) and rigid (7, 9, 11, 13) analogues. Compounds 7, 8, 9, and 11 showed high 5-HT(1A) receptor affinity (K(i) = 4-72 nM). They acted as 5-HT(1A) postsynaptic receptor antagonists, since, like 1, they inhibited the behavioral syndrome, i.e., flat body posture (FBP) and forepaw treading (FT), in reserpine-pretreated rats as well as the lower lip retraction (LLR) in rats, both induced by 8-hydroxy-2-(di-n-propylamino)tetralin hydrobromide (8-OH-DPAT), a 5-HT(1A) receptor agonist. Compound 12, which demonstrated high 5-HT(1A) receptor affinity (K(i) = 50 nM), revealed properties of a partial 5-HT(1A) receptor agonist: it induced LLR and, at the same time, inhibited FT in rats. Compound 13 (K(i) = 1600 nM) was not tested in a behavioral study. Restriction of the conformational freedom in 2, a full 5-HT(1A) receptor antagonist, yielded compound 14 with high 5-HT(1A) receptor affinity (K(i) = 47 nM) and partial agonist properties at postsynaptic 5-HT(1A) receptors in the above tests in vivo; i.e., it induced LLR and inhibited FBP and FT in rats. New constrained analogues of 1 and 2 (compounds 7 and 14, respectively) were also synthesized to recognize a bioactive conformation of those 5-HT(1A) receptor antagonists. On the basis of in vitro and in vivo investigations, binding and functional properties of compound 7 were found to reflect those of 1 at 5-HT(1A) receptors. On the other hand, compound 14, a rigid analogue of 2, showed a different activity in vivo in comparison with the parent compound. PM3 and MM calculations revealed the existence of three low-energy conformers of 7 and six of 14, all of them belonging to the extended family of conformations. The optimized structures of both analogues had a different angle between aromatic planes of terminal fragments; moreover, the heteroaromatic system of those molecules occupied various space regions. Our present study provides support to the hypothesis that the bioactive conformation of 1, responsible for its postsynaptic 5-HT(1A) receptor antagonism, is an extended linear structure represented by 7.

Animals↗
PubMed1999

Social stress inhibits the nitric oxide effect on the corticotropin-releasing hormone- but not vasopressin-induced pituitary-adrenocortical responsiveness.

Putative involvement of endogenous nitric oxide (NO) in the corticotropin-releasing hormone (CRH, 1 microg/kg i.p.)- and vasopressin (AVP, 5 microg/kg i.p.)-induced ACTH and corticosterone secretion was investigated in both non-stressed and crowded rats. The NO synthase blocker Nomega-nitro-l-arginine (l-NNA, 2 mg/kg i.p. ) significantly augmented the AVP-induced ACTH and corticosterone secretion in control and stressed rats, but it increased the CRH-induced ACTH response only in control rats. Crowding stress did not affect the l-NNA evoked increase in AVP-induced hormone responses, but it abolished the CRH-induced ACTH response.

Animals↗
PubMed1999

Blockade of nitric oxide formation impairs adrenergic-induced ACTH and corticosterone secretion.

It has been suggested that adrenergic agents might modulate the L-arginine-NO pathway. Sympathomimetic agonists enhance the basal release of NO, and noradrenaline increases the synthesis of nitric oxide synthase (NOS) in the medial basal hypothalamus in vitro. In the present study possible involvement of NO in central stimulation of the hypothalamic-pituitary-adrenal (HPA) axis by adrenergic agents was investigated in conscious rats. The nitric oxide synthase blocker N(omega)-nitro-L-arginine methyl ester (L-NAME 2 and 10 microg) was administered intracerebroventricularly (i.c.v.) 15 min before the adrenergic agonist given by the same route; 1 h later the rats were decapitated. Plasma levels of ACTH and corticosterone were measured. L-NAME significantly diminished the ACTH and corticosterone response to phenylephrine (30 microg), an alpha1-adrenergic receptor agonist. These hormone responses to clonidine (10 microg), an alpha2-receptor agonist, were dose-dependently suppressed or totally abolished by L-NAME. A significant rise in the ACTH and corticosterone secretion induced by isoprenaline (10 microg), a beta-adrenergic receptor agonist, was only moderately diminished by pretreatment with L-NAME. These results indicate that NOS is considerably involved in central stimulation of the HPA axis by alpha1- and alpha2-adrenergic receptor agonists, and that NO mediates the stimulatory action of these agonists on ACTH and corticosterone secretion. The stimulation induced by beta-adrenergic receptors is only moderately affected by endogenous NO.

Adrenergic Agonists↗
PubMed1998

Effect of desipramine on immunological parameters in mice, and their reversal by stress.

Immunomodulation of cell-mediated immunity is demonstrated in mice, after administration of desipramine, a noradrenaline-reuptake inhibitor, with or without exposing the mice later to an acute swimming stress. A single i.p. injection of 10 mg/kg desipramine to naive mice increased the relative weight of their spleens, the response of their splenocytes to the mitogen concavaline-A and their ability to produce IL-10, as compared to saline controls. Exposing the desipramine-treated mice to a swimming stress significantly reduced these parameters, as well as the levels of IL-2 and IFN-gamma, as compared to desipramine-treated mice. Stress alone reduced the weight of the spleen, and the ability of splenocytes to produce IFN-gamma. As desipramine and acute stress have stimulatory effect on the sympathetic system, it is suggested that a concomitant administration of the drug and a stressful event of these mice, change the splenocytes' micro-environment of sympathetic transmitters, and inhibit their function. These results may be partially due to impairment in the T-helper cell function by a beta-adrenoreceptor-dependent mechanism.

Animals↗
PubMed1998

Effect of L-NAME, a specific nitric oxide synthase inhibitor, on corticotropin-releasing hormone-elicited ACTH and corticosterone secretion.

This study was designed to determine the role of endogenous nitric oxide (NO) in the corticotropin-releasing hormone (CRH)-induced ACTH and corticosterone secretion, as well as possible involvement of hypothalamic dopamine and noradrenaline in that secretion in conscious rats. CRH given i.p. stimulated dose-dependently the pituitary-adrenocortical activity measured 1 h later. Dexamethasone (0.2 mg/kg i.p.) injected 1 h before CRH (1 microg/kg i.p.) totally abolished the CRH-elicited ACTH and corticosterone secretion, indicating a predominantly pituitary site of CRH-evoked stimulation. L-arginine (120 mg/kg i.p.) and N(omega)-nitro-L-arginine methyl ester (L-NAME 5-10 mg/kg i.p.) did not markedly affect the basal plasma ACTH and corticosterone levels. L-NAME given 15 min before CRH markedly, but not significantly, augmented the CRH-induced ACTH response, and enhanced more potently and significantly the corticosterone response. Pretreatment with L-arginine, a substrate for NOS, slightly diminished the CRH-induced ACTH response and considerably reduced the corticosterone response. L-arginine also significantly reversed the L-NAME-evoked increase in the CRH-induced ACTH and corticosterone secretion. L-NAME did not markedly alter the CRH-induced hypothalamic dopamine and noradrenaline levels, while L-arginine significantly increased noradrenaline level. However, those alterations were not directly correlated with the observed changes in ACTH and corticosterone secretion. These results indicate that in conscious rats NO plays a marked inhibitory role in the CRH-induced ACTH secretion and inhibits more potently corticosterone secretion. Hypothalamic dopamine and noradrenaline do not seem to be directly involved in the observed alterations in ACTH and corticosterone secretion.

Adrenocorticotropic Hormone↗
PubMed1998

Influence of nitric oxide synthase inhibitors on the vasopressin-induced pituitary-adrenocortical activity and hypothalamic catecholamine levels.

In the present study the role of endogenous nitric oxide (NO) in the vasopressin-induced ACTH and corticosterone secretion was investigated in conscious rats. Vasopressin (AVP 5 microg/kg i.p.) considerably augmented ACTH and corticosterone secretion. L-arginine (120 and 300 mg/kg i.p.) did not significantly alter the AVP-induced secretion of those hormones. Nitric oxide synthase (NOS) blockers N(omega)-nitro-L-arginine (L-NNA) and its methyl ester (L-NAME) given i.p. 15 min before AVP markedly increased the AVP-induced ACTH secretion. L-NNA (2 mg/kg) more potently and significantly increased the AVP-induced ACTH secretion, whereas L-NAME elicited a weaker and not significant effect. Both those NOS antagonists intensified significantly and to a similar extent the AVP-induced corticosterone secretion. L-arginine (120 mg/kg i.p.) reversed the L-NNA-induced rise in the AVP-stimulated ACTH secretion and substantially diminished the accompanying corticosterone secretion. Neither vasopressin alone nor in combination with L-arginine and L-NAME evoked any significant alterations in the hypothalamic noradrenaline and dopamine levels. L-NNA (2 and 10 mg/kg i.p.) elicited a dose dependent and significant decrease in the hypothalamic noradrenaline level. The hypothalamic dopamine level was not significantly altered by any treatment. These results indicate that in conscious rats endogenous NO has an inhibitory influence on the AVP-induced increase in ACTH and corticosterone secretion. L-NNA is significantly more potent than L-NAME in increasing the AVP-induced ACTH secretion. This may be connected with a considerable increase by L-NNA of hypothalamic noradrenergic system activation which stimulates the pituitary-adrenal axis in addition to specific inhibition of NOS.

Adrenocorticotropic Hormone↗
PubMed1998

Effect of indomethacin on nicotine-induced ACTH and corticosterone response.

The effect of nicotine on ACTH and corticosterone secretion and possible mediation of prostaglandins in this secretion was investigated in conscious rats. Nicotine (5 and 10 mg/kg i.p.) considerably increased the plasma ACTH and corticosterone levels, measured 1h after injection. Mecamylamine (10 and 50 micrograms i.c.v.), a nicotinic receptor antagonist, given 15 min prior to nicotine dose-dependently diminished the ACTH and corticosterone responses, by 59 and 30% respectively. Pretreatment with hexamethonium (2 mg/kg i.p.), a peripheral blocker of nicotinic receptors, diminished to a similar extent the nicotine-induced ACTH and corticosterone responses. On the other hand atropine, a muscarinic receptor antagonist, did not markedly alter those responses. Systemic or intracerebroventricular pretreatment with indomethacin (2 mg/kg i.p. or 0.1 and 1 microgram i.c.v.), a cyclooxygenase and endogenous prostaglandin synthesis blocker considerably reduced, by 58%, the nicotine-induced ACTH response, but did not alter the corticosterone response. These results show that nicotine given systemically stimulates ACTH and corticosterone secretion by selective activation of central and peripheral acetylcholine nicotinic receptors. Endogenous prostaglandins are significantly involved in the nicotine-induced central stimulation of ACTH secretion. Prostaglandins do not directly affect the nicotine-induced corticosterone secretion from the adrenal cortex.

Adrenocorticotropic Hormone↗
PubMed1998

Involvement of the central noradrenergic system in cholinergic stimulation of the pituitary-adrenal response.

Involvement of the central adrenergic system in stimulation of the hypothalamic-pituitary-adrenal (HPA) axis by carbachol, a cholinergic muscarinic agonist, was assessed indirectly through corticosterone secretion. Carbachol (2 micrograms) given intracerebroventricularly or intraperitoneally evoked a dose-related increase in serum corticosterone levels. On a molar basis, carbachol given i.c.v. was considerably more active than when injected i.p., indicating its central site of action. The corticosterone response to i.c.v. carbachol was significantly reduced by pretreatment of rats 15 min earlier with prazosin, an alpha 1-adrenergic receptor antagonist. Pretreatment with yohimbine, an alpha 2-adrenergic antagonists, did not significantly affect the carbachol-induced corticosterone response. Propranolol, a beta-adrenergic blocker, given i.c.v. or i.p. significantly impaired the carbachol-elicited corticosterone secretion. The selective noradrenergic neurotoxin DSP-4 (50 mg/kg) given i.p. 8 days before the experiment, also potently diminished the carbachol-induced rise in serum corticosterone levels. Carbachol markedly increased, while DSP-4 significantly diminished the hypothalamic noradrenaline levels. Likewise, DSP-4 significantly impaired the carbachol-induced rise in hypothalamic noradrenaline levels. Our present results indicate that the central adrenergic system is involved in the cholinergic muscarinic stimulation of the pituitary-adrenocortical response. Both hypothalamic noradrenaline and adrenergic alpha 1- and beta-receptors are significantly involved in the carbachol-induced HPA response.

Adrenergic Antagonists↗
PubMed1997

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↗
PubMed1997

Role of nitric oxide in the vasopressin-induced corticosterone secretion in rats.

The presence of nitric oxide synthase (NOS) in hypothalamic structures which control the activity of the hypothalamic-pituitary-adrenal (HPA) axis suggests a role for NO in regulation of ACTH and corticosterone secretion. We investigated the involvement of NO in the corticosterone secretion induced by vasopressin (AVP), a potent coregulator of the HPA activity. AVP injected i.p. was, on a molar basis, considerably more potent than administered intracerebroventricularly in inducing corticosterone secretion. This finding suggests a preferential action of AVP on pituitary corticotrop receptors, but not on central structures involved in stimulation of the HPA axis. Dexamethasone given before AVP totally abolished the AVP-elicited corticosterone response by a feedback mechanism and/or inhibition of the phospholipase A2 activity and prostaglandin synthesis. Pretreatment with the NOS inhibitors L-NAME and L-NNA augmented significantly and to a similar extent the corticosterone response to AVP administered both systemically and centrally and L-NNA was found to be more potent in this respect. Pretreatment with L-arginine markedly reduced the AVP-induced corticosterone response. These results suggest that endogenous nitric oxide is significantly involved in the AVP-elicited corticosterone secretion and NO-induced alterations in the prostaglandin synthesis may participate in this action.

Animals↗
PubMed1996

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↗
PubMed1996

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↗
PubMed1996

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↗
PubMed1996

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↗
PubMed1995

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↗