Biomedical subjects

B Mravec

Publications and source records attributed to B Mravec.

15 recordsLinked to original sources

PubMed2006

The peripheral noradrenergic terminal as possible site of action of salsolinol as prolactoliberin.

Salsolinol, an endogenous isoquinoline, induces selective prolactin release in rats [Tóth, B.E., Homicskó, K., Radnai, B., Maruyama, W., DeMaria, J.E., Vecsernyés, M., Fekete, M.I.K., Fülöp, F., Naoi, M., Freeman, M.E., Nagy, G.M., 2001. Salsolinol is a putative neurointermediate lobe prolactin releasing factor. J. Neuroendocrinol. 13, 1042-1050]. The possible role of dopaminergic and adrenergic signal transduction was investigated to learn the mechanism of this action. The effect of salsolinol (10mg/kg i.v.) was inhibited by reserpine treatment (2.5mg/kg i.p.) and reinstated by pretreatment with monoamine oxidase inhibitor (pargyline 75 mg/kg i.p.). Salsolinol did not affect the in vitro release of dopamine (DA) in the median eminence, and did not inhibit the L-DOPA induced increase of DA level in the median eminence. 1-Methyl dihydroisoquinoline (1MeDIQ) is an antagonist of salsolinol induced prolactin release and causes increase in plasma NE level [Mravec, B., Bodnár, I., Fekete, M.I.K., Nagy, G.M., Kvetnansky, R., 2004. An antagonist of prolactoliberine induces an increase in plasma catecholamine levels in the rat. Autonom. Neurosci. 115, 35-40]. Using tissue catecholamine contents as indicators of the interaction between salsolinol and 1MeDIQ we found no interaction between these two agents to explain the changes in prolactin release in the median eminence, lobes of the pituitary, superior cervical and stellate ganglion. Increasing doses of salsolinol caused a dose dependent decrease of tissue dopamine concentration and increase of NE/DA ratio in the salivary gland, atrium and spleen. These changes of DA level and NE/DA ratio run parallel in time with the increase of prolactin release. 1MeDIQ antagonized the increase of prolactin release and decrease of tissue DA content caused by salsolinol. Neither this increase of prolactin secretion nor the decrease of DA level in spleen could be demonstrated in NE transporter (NET) knock out mice. The results presented argue for the possible role of peripheral norepinephrine release as a target for salsolinol in its action releasing prolactin. The dominant role of norepinephrine transporter may be suggested.

Animals↗

PubMed2006

Does vagus nerve constitute a self-organization complexity or a "hidden network"?

The vagus nerve provides wide visceromotor and viscerosensory innervation of internal organs. Findings accumulated in last years suggest that vagus nerve participates on regulation of much wider spectrum of functions than described previously. Many different studies provide plausible evidence that vagus nerve importantly participates not only in transmission of information from inflamed tissues, but also in efferent modulation of inflammatory processes. Moreover, there are some findings supporting the hypothesis that vagus nerve might participates in monitoring and modulation of tumorigenesis. Electrical stimulation of the vagus nerve is used as a treatment of epilepsy. Moreover, data also suggest a beneficial effect of electrical stimulation of the vagus nerve in patients with depression, anxiety, migraine and Alzheimer's disease. We suggest, that the vagus nerve might constitute a highly differentiated complex system which modulates various functions. Moreover, we propose that the vagus nerve as a complex system might participate in constitution of a biological compartment of conscious. In this article we discuss findings and ideas supporting these hypotheses (Ref. 73).

Electric Stimulation Therapy↗

PubMed2006

Complex intracardiac nervous system.

The heart is an organ with continuous activity, which must satisfy demands of an organism on various conditions. Therefore, heart activity is modulated at many levels, including intrinsic regulatory mechanisms, humoral factors and autonomic nervous system. The regulation of heart activity by sympathetic and parasympathetic nervous system is well known. Accumulated evidence in recent decades indicates that intracardiac neurons can also significantly regulate heart activity. These neurons are concentrated in multiple heart ganglia. Interactions between neurons within intracardiac ganglia together with interconnections between individual ganglia provide anatomical and functional basis of complex nervous network of the heart. This complex intracardiac nervous system together with extracardiac autonomic neurons, innervating heart, provides modulation of heart activity during both physiological and pathological conditions. This review article summarizes recent knowledge about the role of heart neurons in physiological conditions and in etiopathogenesis of selected diseases. Effect of pharmacological and surgical interventions on heart neurons is also discussed (Fig. 2, Ref. 70).

Heart↗

PubMed2006

Chronic polysystemic candidiasis as a possible contributor to onset of idiopathic Parkinson's disease.

The underlying cause of Parkinson's disease is still enigma. Several mechanisms have been implicated in the etiopathogenesis of PD including oxidative damage, environmental toxins, genetic predisposition, and accelerated aging. Recent research suggests that salsolinol, a derivate of dopamine, is an important contributing factor. In the presence of acetaldehyde dopamine is converted into salsolinol, a neurotoxin involved in apoptosis of dopaminergic neurons. Increased production of acetaldehyde is associated with chronic polysystemic candidiasis (CPC). Chronically elevated levels of acetaldehyde in patients with CPC might participate in the formation of salsolinol and its metabolites in the brain contributing to the destruction of dopaminergic cells in substantia nigra. Clinical mental symptoms of PD often correspond with the mental manifestations of CPC. This hypothesis may constitute basis for further scientific and clinical research of PD etiopathogenesis (Fig. 1, Ref. 29).

Acetaldehyde↗

PubMed2005

Salsolinol, a derivate of dopamine, is a possible modulator of catecholaminergic transmission: a review of recent developments.

Catecholamine (dopamine, norepinephrine and epinephrine) synthesizing neurons are widely distributed in the brain, sympathetic ganglia and throughout peripheral organs. Results of several recent experiments clearly suggest that many of these neurons can also contain 1-methyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline (salsolinol), a derivate of dopamine. However, direct proof of salsolinol synthesis in those neurons is still missing. The data obtained with administration of exogenous salsolinol strongly indicate that it may play an important role in catecholaminergic regulatory processes, such as the regulation of prolactin release and/or neuronal transmission in sympathetic ganglia. Several recent data have also indicated a relationship between salsolinol or its metabolites and the etiology of Parkinson's disease or neuropathology of chronic alcoholism. These seemingly different roles of salsolinol will be discussed separately, but some common features will also be highlighted. Based on all of the discussed data the existence of a "salsolinolergic" system using salsolinol as a neuromodulator, which may be present in catecholamine synthesizing neurons, is postulated.

Animals↗

PubMed2005

Distinct modulation of a gene expression of the type 1 and 2 IP(3) receptors by retinoic acid in brain areas.

Inositol 1,4,5-trisphosphate (IP(3)) receptors belong to the intracellular calcium channels that release calcium from the intracellular stores after binding IP(3). Three types of IP(3) receptors occurred in a tissue specific manner and different promoters direct their gene expression. Thus, understanding of the transcriptional regulation is the first step towards comprehension of the function of these receptors. Since the retinoic acid activates RARE and AP2 transcription factors, the present study focuses on determination of whether or not expression of type 1 and 2 IP(3) receptors is modulated by retinoic acid in selected brain areas. We have found that mRNA levels of the type 1 IP(3) receptors were decreased significantly in cerebellum and hypothalamus, but not in the brain stem of rats treated with retinoic acid, compared to untreated littermates. The mRNA levels of the type 2 IP(3) receptor were significantly decreased in all tested tissues, cerebellum, hypothalamus, and also in brain stem after the treatment with retinoic acid. These results show that gene expression of both type 1 and 2 IP(3) receptors is regulated by retinoic acid, although the effect of retinoic acid on mRNA levels of the type 1 IP(3) receptors is dependent on brain area.

Animals↗

PubMed2005

Phenylethanolamine N-methyltransferase gene expression in transplanted human heart.

BACKGROUND: Phenylethanolamine N-methyltransferase (PNMT) is an enzyme involved in the epinephrine synthesis. The aim of this study was to investigate PNMT gene expression in the transplanted human heart in relation to the time elapsed from heart transplantation (HTx) and selected clinical characteristics. PATIENTS AND METHODS: The messenger RNA (mRNA) levels of PNMT in myocardial tissue were determined in 22 (21 males) patients at 0-12 years after HTx. Relative quantification of mRNA levels was performed using reverse transcription and polymerase chain reaction (RT-PCR) for correlation with heart rate (HR), blood pressure (BP), parameters of heart rate variability, and graft systolic and diastolic functions. RESULTS: During the first 3 years after HTx, PNMT mRNA levels were higher (mean +/- SEM) (0.75 +/- 0.06; n = 12) compared with later years (0.33 +/- 0.06; n = 10); (P < .01). HR variability in the low frequency band of the power spectrum (LF) was lower among patients during the first 3 years after HTx (2.73 +/- 0.31 vs 5.67 +/- 0.69 ms; P < .01). A significant negative linear correlation was observed between PNMT mRNA and LF (P = .05; r = -0.47). No association was noted between HR, BP, parameters of systolic or diastolic function, standard deviation of all RR intervals, or high frequency (0.15-0.40 Hz) bands of the 24-hour RR interval power spectrum. CONCLUSION: This work provides the first evidence of the presence of local PNMT transcription in human heart after HTx. Appearance of PNMT transcription in the myocardium after HTx may reflect autonomous "sympathicotrophy." Decreased PNMT expression with time elapsed after HTx suggests graft reinervation.

Blood Pressure↗

PubMed2005

Formalin attenuates the stress-induced increase in plasma epinephrine levels.

Subcutaneous (s.c.) injection of formalin into rats is frequently used as a painful stressor that produces a three-phase nociceptive response. We have shown previously that s.c. administered formalin (0.2 ml of 4% solution per 100 g body weight) unexpectedly attenuated the increase of plasma epinephrine levels in rats exposed to exteroceptive stressors (handling, immobilisation). To clarify the mechanism(s) responsible for this phenomenon, the effect of formalin applications on epinephrine plasma levels was investigated in various experimental conditions. Subcutaneous application of formalin combined with exposures of animals to an interoceptive stressor, insulin-induced hypoglycaemia, significantly attenuated the stress-induced increase in plasma epinephrine levels, whereas plasma norepinephrine levels remained highly elevated. Moreover, administration of formalin to unstressed animals also manifested signs of an attenuated epinephrine secretion. Interestingly, intraperitoneal administration of formalin did not reduce the elevated levels of plasma epinephrine. We suggest that formalin attenuates epinephrine secretion from the adrenal medulla most probably via irritation of s.c. somatosensory receptors. We hypothesise that the irritation of the primary sensory afferents fibres might reduce the activity of the sympathetic preganglionic neurones innervating adrenal medullary chromaffin cells. Further investigations are required to establish whether the observed reduction of epinephrine secretion from the adrenal medulla is controlled by either spinal or supraspinal neuronal circuits.

Animals↗

PubMed2004

Fos protein expression in mouse hypothalamic paraventricular (PVN) and supraoptic (SON) nuclei upon osmotic stimulus: colocalization with vasopressin, oxytocin, and tyrosine hydroxylase.

The quantity and topography of activated vasopressin (AVP), oxytocin (OXY), and tyrosine hydroxylase (TH) neurons were studied immunohistochemically in the anterior, middle, and posterior portions of the PVN and SON in mice 60 min after a single injection of hypertonic saline (HS, 400 microl 1.5M, i.p.). Fos-neuropeptide double-stainings revealed: (1) Fos expression in each portion of the PVN and SON; (2) maximal number of Fos-AVP (79 cells) and Fos-OXY (50 cells) double-labelings in the middle portion of the PVN; (3) low number of Fos-TH perikarya in the PVN and their lack in the SON; (4) similar incidence (around 50%) of Fos-AVP and Fos-OXY perikarya in the SON; and (5) presence of activated AVP, OXY, and TH neurons in the periventricular, subependymal, and sub-PVN zones of the PVN. Topographic analysis revealed that the majority of AVP neurons expressing Fos occupied the dorsolateral and central part of the middle portion of the PVN. In the same PVN portion, Fos-OXY neurons occurred in similar frequency, however, they were primarily distributed along the lateral and medial margins of the PVN. In the SON, Fos-OXY cells occupied mainly its dorsal, while Fos-AVP cells predominated in its ventral part. The data clearly indicate that HS is not a selective stimulus neither for PVN nor SON itself and provide evidence that both PVN and SON AVP and OXY cells play important role in the mediation of signals induced by HS. In addition, the limited number of AVP, OXY, and TH neurons activated by HS may account for their differential functional specializations selective for stress/osmotic circuits activated by HS.

Animals↗

PubMed2004

Stress- as well as suckling-induced prolactin release is blocked by a structural analogue of the putative hypophysiotrophic prolactin-releasing factor, salsolinol.

Prolactin is secreted from the anterior lobe of the pituitary gland in response both to suckling and to stress. We recently observed that 1-methyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline (salsolinol), produced in the neurointermediate lobe of the pituitary gland, as well as in the medial basal hypothalamus, can selectively release prolactin from the anterior pituitary. Therefore, it has been proposed that salsolinol is a putative endogenous prolactin-releasing factor (PRF). Here, we report that one structural analogue of salsolinol, 1-methyl-3,4-dihydroisoquinoline (1MeDIQ), can block salsolinol-induced release of prolactin, but does not affect prolactin release in response to thyrotropin releasing hormone (TRH), alpha-methyl-p-tyrosine (alpha MpT) (an inhibitor of tyrosine hydroxylase), domperidone (a D(2) dopamine receptor antagonist), or 5-hydroxytryptophan (5-HTP), a precursor of serotonin). 1MeDIQ profoundly inhibited suckling-, immobilization-, as well as formalin-stress induced prolactin release without any influence on corticosterone secretion. The 1MeDIQ-induced reduction in prolactin response to immobilization stress was dose-dependent. These results suggest that salsolinol can play a pivotal role in the regulation of prolactin release induced by either physiological (suckling) or environmental (stress) stimuli.

Adaptation, Physiological↗

PubMed2004

Inhibitory effect of formalin administration on immobilization-induced epinephrine release.

Injection of formalin is used as a classical painful stressor that produces a biphasic nociceptive response consisting of a 1- to 10-min early phase and a later phase 30 to 240 min after injection. The period between these two phases, called "interphase," is characterized by attenuated nociception. We evaluated the response of catecholamine plasma levels to formalin-induced pain stress with special attention to these three time periods. Subcutaneous injection of 4% formalin (0.2 mL/100 g bw) into the hind limb produced a slight reduction of plasma epinephrine levels in the first 15 min, which was followed by a significant increase that remained high up to 120 min after injection. Norepinephrine levels increased immediately after injections and remained high from 30 until 120 min. To test the effect of formalin injection in a stressful condition, we exposed animals to 2 h immobilization stress. In the first experiment, formalin was injected before the start of immobilization. A significant decrease of plasma epinephrine levels was measured up to 25 min post-injection, whereas plasma norepinephrine levels remained high. A second formalin injection during immobilization was as effective as the first one: It depleted plasma epinephrine levels from 5 to 15 min post-injection without significant changes in norepinephrine levels. In the second experiment, formalin given after the beginning of immobilization produced a significant decrease of epinephrine levels 15 min after the injection and produced a significant increase 60 min after injection. The plasma norepinephrine levels were significantly increased by 40 min post-injection. The data show that the inhibitory process during the interphase of formalin test is able to significantly decrease epinephrine release not only during basal conditions but also during exposure to a severe stressor, such as immobilization without suppression of plasma norepinephrine levels.

Animals↗

PubMed2004

Pivotal role of an endogenous tetrahydroisoquinoline, salsolinol, in stress- and suckling-induced release of prolactin.

In mammals, the role of a prolactin-releasing factor (PRF) in the acute changes of prolactin (PRL) secretion that usually occur after challenges (e.g., suckling stimulus or stress) of homeostasis has been suspected for a long time. We have recently observed that 1-methyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline, salsolinol (SAL), produced by the hypothalamus and the neuro-intermediate lobe (NIL) of the pituitary gland, can selectively release PRL from the anterior lobe (AL). Moreover, binding sites for SAL have been detected in areas like median eminence, NIL, and AL. It has been proposed that SAL is a putative endogenous PRF. We have also found that a structural analogue of SAL, 1-methyl-3,4-dihydroisoquinoline (1MeDIQ), is able to block dose-dependently SAL-, suckling-, and immobilization (IMO) stress-induced release of PRL without having any influence on alpha-methyl-p-tyrosine (alphaMpT)-induced PRL responses. Neither SAL nor 1MeDIQ has any effect on alpha-melanocyte-stimulating hormone (alphaMSH), adrenocorticotrophic hormone (ACTH), beta-endorphin (beta-END) and arginine-vasopressin (AVP) secretion. Moreover, SAL-induced PRL response was attenuated in male rats pretreated with dexamethasone (DEX). These results strongly suggest that SAL has an important role in the regulation of PRL release induced by physiologic and environmental stimuli; therefore, it can be considered as the strongest candidate for being the PRF in the hypothalamo-hypophysial system. Our findings also indicate that the adrenal steroids may play an inhibitory feedback role in SAL-mediated PRL response.

Animals↗

PubMed2004

Quantitative evaluation of catecholamine enzymes gene expression in adrenal medulla and sympathetic Ganglia of stressed rats.

Stress-induced changes in mRNA levels of tyrosine hydroxylase (TH), dopamine-beta-hydroxylase (DBH), and phenylethanolamine N-methyltransferase (PNMT) have been expressed as relative arbitrary units compared with a control group. The aim of this study was to quantify basal and stress-induced levels of TH, DBH, and PNMT mRNAs in rat adrenal medulla (AM) and stellate ganglia (SG) by the RT-competitive PCR method using corresponding competitors of known concentration. In rats stressed by immobilization (IMO) once for 2 h, the concentration of mRNAs was determined in various intervals after the end of stress stimulus. In SG, the basal concentration of TH mRNA was 0.017 amol/ng of total RNA, which is approximately 30 times lower than in the AM (0.460 amol/ng RNA). The basal concentration of DBH mRNA in SG was 2.60 amol/ng of total RNA, which is about 150 times more than TH mRNA in SG but only two times less than DBH mRNA in the AM in which PNMT mRNA is present in the highest concentration. After a single 2-h IMO, the peak elevation of TH and DBH mRNA concentration in SG occurred 24 h after the termination of stress stimulus, when their AM mRNA concentrations were already at control values. Presence of PNMT mRNA levels in the SG, of control and stressed rats has been demonstrated for the first time. Repeated IMO (7 days, 2 h daily) did not produce further increase in the mRNA concentrations compared with the elevated values found in adapted control groups. Levels of TH protein were significantly increased only after repeated IMO in SG and AM. Thus, our data show for the first time the exact concentrations of TH, DBH, and PNMT mRNA in SG and AM of rats under control and stress conditions. The lowest concentration of TH mRNA in the AM and SG supports the hypothesis that tyrosine hydroxylation is the rate-limiting step in catecholamine biosynthesis.

Adrenal Medulla↗

PubMed2004

Effect of 6-hydroxydopamine on the gene expression of Na+/Ca2+ exchanger in the rat heart.

The Na+/Ca2+ exchanger (NCX) is an important component of the process of excitation-contraction coupling in the heart muscle. The level of gene expression as well as transport activities of this membrane structure is changed under pathological conditions like ischemic injury, myocardial infarction or diabetes. In this work we focused on the question whether the adrenergic modulation affects gene expression of the NCX in rat hearts. NCX mRNA levels were studied in the left cardiac atrium (divided into ganglionic and nonganglionic part) and also in the left ventricle of rats treated with 6-hydroxydopamine (6-OHDA) in control and stressed conditions. We have shown that administration of 6-OHDA decreases mRNA levels of NCX in both ganglionic and nonganglionic part of the left atrium and also in the left ventricle. This effect was not altered under combined administration of 6-OHDA and single immobilization stress. These data suggest that an activation of the adrenergic system can potentiate gene expression of the cardiac NCX.

Animals↗

PubMed2004

[The brain catecholamines: brief anatomy and participation in the stress reaction and regulation of cardiovascular function].

Catecholamines (norepinephrine, dopamine, epinephrine) act in the brain as chemical neurotransmitters and represent integrative component of many anatomical and functional interrelationships, which play important role in the maintenance of the basic physiological processes and homeostasis of living organism. In the brain, several well circumscribed conglomerations of catecholaminergic neurons and dopaminergic and noradrenergic pathways can be recognized. Although they are represented by only a few thousands of catecholaminergic neurons (in rat about 5) located only in certain brain areas, their rich arborization provides extensive innervation over the whole brain. Catecholamines are significantly involved in conveying of viscero- and somato-sensitive signals to integrative centrers located in higher brain areas and participate in the regulation of all vitally important systems under basal conditions as well as during stress. Their normal physiological activity is important for the maintenance of healthy functioning of the organism. Brainstem aggregations of catecholaminergic neurons, localized predominantly in autonomic regions, are involved in conveying the afferent peripheral stress and cardiovascular signals. The hypothalamic paraventricular nucleus, which represents an integrative center of the stress response, receives a rich catecholaminergic innervation from the caudal brain. On the other hand, catecholaminergic neurons localized in the ventrolateral rostral medulla form an important component of circuits involved in the regulation of the cardiovascular system. Central catecholamines are also involved in many other important brain circuits, however, with respect to the limited space of this review, they could not be included.

Animals↗