It has been reported previously that systemic administration of clonidine, an agonist of α-2 receptors for noradrenaline, significantly retards amygdaloid kindling, by delaying the emergence from partial seizure, Conversely, systemic administration of α-2 antagonists has been reported to facilitate amygdaloid kindling, The experiments I conducted attempted to discover whether α-2 adrenoceptors in the amygdala participated in these effects, I examined the effect of either systemic administration (i,p.) or intraamygdaloid infusions of a variety of noradrenergic drugs on the kindling of seizures with electrical stimulation of the amygdala, Rats received either low-frequency stimulation of the amygdala, to induce rapid kindling, or conventional high-frequency stimulation, Drugs and electrical stimulation were administered once every 48 hrs, I observed a significant retardation of kindling in rats receiving i,p. injections of clonidine (0.1 mg/kg) or unilateral infusions of clonidine in concentrations of [special characters omitted] to [special characters omitted] M, regardless of the stimulation frequency. The prophylactic effect was due to a delay in the progression out of partial seizure. I observed similar effects with infusions of xylazine, also an α-2 adrenoceptor agonist, The effect was specific to the amygdala/pyriform region, because infusions of clonidine dorsal lo the amygdala were without effect. Power spectral analysis of the AD from the stimulated and the contralateral amygdala during the initial occurrence of bilateral AD failed to reveal differences attributable to clonidine, Therefore, clonidine might retard kindling by modifying the propagation of AD from the stimulated amygdala to a midbrain or pontine brainstem area critical, for the expression of generalized seizures. Clonidine had no effect on established generalized seizures, suggesting that it was producing a genuine prophylactic effect against kindling. Unexpectedly, intraamygdaloid infusions of either idazoxan, yohimbine, or SK&F 104856, antagonists of α-2 receptors, failed to accelerate kindling. Simultaneous infusion of idazoxan blocked clonidine’s prophylactic effect, which suggests strongly that this effect was mediated at the α-2 adrenoceptor. Blockade of amygdaloid α-1 adrenoceptors with corynanthine failed to affect kindling. I conclude that the population of α-2 adrenoceptors in the amygdala/pyriform region contributes to the antiepileptogenic effect observed after systemic administration of clonidine and that the facilitation of kindling observed after systemic administration of α-2 antagonists reported previously may have been mediated by the blockade of a population of α -2 adrenoceptors in addition to, or outside of, the amygdala/pyriform region. / Graduate

No description available.

Orientador: André Sampaio Pupo / Banca: Ana Lúcia Severo Rodrigues / Banca: Ricardo Luiz Nunes de Souza / Banca: Márcia Gallacci / Banca: Leonardo Resstel Barbosa Moraes / Resumo: A imipramina é antidepressivo tricíclico cujo principal mecanismo é a inibição da captura neuronal de noradrenalina e/ou serotonina, aumentando os níveis sinápticos dessas monoaminas. Além disso, a imipramina, bem como outros antidepressivos tricíclicos, antagonizam os adrenoceptores α1 na mesma faixa de concentração em que inibem o transportador de noradrenalina. Por outro lado, estudos recentes mostraram que a imipramina tem afinidades distintas para os três subtipos de adrenoceptores α1, (α1A, α1B e α1D), ou seja, aproximadamente 25 vezes mais seletiva para α1A em relação aos adrenoceptores α1B e 10 vezes para adrenoceptores α1D em relação aos adrenoceptores α1B. Isso sugere que seu mecanismo de ação possa estar relacionado com essa característica, uma vez que, ao aumentar os níveis sinápticos de noradrenalina, antagoniza α1A e α1D, mas deixa relativamente livre α1B. Então, o objetivo desta tese foi investigar a participação dos adrenoceptores α1A, α1B e α1D no efeito anti-imobilidade da imipramina no teste de suspensão pela cauda em camundongos. Para isso, camundongos foram submetidos ao teste de suspensão pela cauda, com a administração de diversos antagonistas seletivos e não-seletivos para subtipos α1. Os testes foram realizados utilizando a imipramina associada ao prazosin, antagonista não-seletivo para adrenoceptores α1, RS-100329, antagonista seletivo pra α1A, L-765314, seletivo par α1B e BMY-7378, seletivo para α1D. Os animais também foram avaliados com administrações únicas dos antagonistas. Esta tese mostrou que a administração concomitante de prazosin ou o L-765314 reverteram o efeito anti-imobilidade da imipramina. Por outro lado, nem o RS-100329 ou BMY-7378 modificaram o efeito anti-imobilidade da imipramina. Além disso, a administração de apenas o RS-100329 ou BMY-7378 apresentou efeito anti-imobilidade no teste de suspensão pela cauda. Isso indica que o efeito ... / Abstract: Imipramine is a tricyclic antidepressant inhibitor of norepinephrine and serotonin neuronal reuptake. In addition, the imipramine antagonizes α1-adrenoceptors in the same concentration range that inhibited norepinephrine transporter. However, the imipramine has different affinity to α1-adrenoceptor subtypes presenting higher affinity (10-25-fold) towards α1A- and α1D-adrenoceptors compared to α1B-adrenoceptors. This study investigates the α1-adrenoceptor subtypes involved in the anti-immobility effect of imipramine in the tail suspension test in mice. The anti-immobility effect of imipramine was significantly antagonized by the non-subtype-selective α1-adrenoceptor antagonist prazosin. Neither the selective α1A adrenoceptor antagonist RS-100329 nor the selective α1D-adrenoceptor antagonist BMY-7378 changed the anti-immobility effect of imipramine. However, the selective α1B-adrenoceptor antagonist L-765314 antagonized the anti-immobility effect of imipramine. In addition, mice treated only with RS-100329 or BMY-7378 showed reduced immobility time in comparison to mice treated with vehicle, whereas L-765314 increased the immobility time. These results suggests that the α1B-subtype is the main target for the increased levels of norepinephrine caused by imipramine, and that the selective antagonism of α1A- and α1D-adrenoceptors results in anti-immobility effects / Doutor

This study examined the effects of epinephrine, norepinephrine, AVP and ACh on fluid movement by the lungs of the late-term guinea pig fetus. Catecholamines and AVP are secreted in high amounts by the fetus during delivery, and could be important with respect to fetal lung fluid removal; this event is vital at the time of birth. The lungs were supported in vitro for a duration of three hours, and production rates were measured using a dye-dilution technique. The average resting production rate in terms of ml/kg‧h declined with gestational age (54-67 days gestation; n=171). There was a lesser decline in the average resting production rate in terms of ml/h. The average production rate of untreated preparations in the first hour was 1.60 ± 0.26 ml/kg body weight per hour, and rates did not change significantly during the remaining two hours of experimentation (n=30). This rate is comparable to those reported from chronically catheterized fetal sheep. Treatment was administered during the second hour of experimentation, following an ABA design. Lungs (n=36) were transferred to fresh Krebs-Henseleit saline containing one of the following concentrations of epinephrine: (a) 10‾⁵ M; (b) 10‾⁶ M; (c) 10‾⁷ M; (d) 5 x 10‾⁸ M; (e) 10‾⁸ M; and (f) 10‾⁹ M. With the exception of the top dose, epinephrine treatment caused an immediate reduction in fluid secretion, or fluid reabsorption. Sodium followed the movement of water in all cases. The effect of epinephrine at 10‾⁷ M was maximal, and the threshold dose for epinephrine was calculated at 1.78 x 10‾¹¹ M. Phentolamine and propranolol had no effect in control preparations. However, phentolamine completely blocked the effect of epinephrine, whereas propranolol was ineffective. Isoproterenol had no effect on pulmonary fluid production. Alpha-adrenergic receptors apparently mediate the effect of epinephrine on pulmonary fluid movement in the fetal guinea pig lung. This conclusion is different from that obtained in fetal sheep, in which beta-adrenergic receptors are utilized. A possible synergism between epinephrine and AVP was examined. Lungs (n=12) were transferred to fresh Krebs-Henseleit saline containing either (a) 0.6 mU/ml AVP, or b) 0.6 mU/ml AVP combined with epinephrine at 10‾⁷ M. Treatment with AVP caused a slow, prolonged reduction in fluid production. Treatment with AVP together with epinephrine did not demonstrate synergism. The effect of norepinephrine (NE) was examined. Lungs (n=36) were transferred to fresh Krebs-Henseleit saline containing one of the following concentrations of NE: (a) 1.24 x 10‾⁵ M; (b) 1.24 x 10‾⁶ M; (c) 1.24 x 10‾⁷ M; (d) 5.24 x 10‾⁸ M; (e) 1.24 x 10‾⁸ M; and (f) 1.24 x 10‾⁹ M. In all preparations, treatment with NE resulted in an immediate reduction in fluid production, and reabsorptions were observed at the higher doses. Sodium followed the movement of water in every case. The threshold dose was calculated at 3.16 x 10‾¹⁰ M. Phentolamine blocked the effect of NE, reinforcing the importance of pulmonary alpha-adrenergic receptors in the fetal guinea pig. There was no relationship between age and degree of response with treatment of either epinephrine or NE, but fetuses under 78.0 g did not respond to NE. The effect of ACh was examined. Lungs (n=24) were transferred to fresh Krebs-Henseleit saline containing one of the following concentrations of ACh: (a) 10‾⁴ M; (b) 10‾⁵ M; (c) 10‾⁶ M; and (d) 10‾⁸ M. At the three top doses, immediate and powerful reabsorptions of pulmonary fluid were observed in older fetuses (60 days gestation and above); significant falls were observed in the younger fetuses. This result was unexpected, as it was hypothesized that ACh would stimulate fluid production. The threshold dose for ACh was between 10‾⁶ M and 10‾⁸ M. Phentolamine blocked the effect of ACh. This result suggested that reabsorption is a result of an indirect effect of ACh acting through pulmonary alpha receptors. The results in this study show that epinephrine, NE, AVP and ACh are all important promoters of fetal pulmonary fluid removal in the fetal guinea pig. Pulmonary alpha-adrenergic receptors mediate the effects of epinephrine, NE and ACh (indirectly). The conclusions drawn from this study emphasize the importance of species' comparison in fetal research. LIST OF ABBREVIATIONS AVP Arginine Vasopressin NE Norepinephrine DOPA dihydroxyphenylalanine PNMT Phenylethanolamine n-methyltransferase ACh Acetylcholine / Science, Faculty of / Zoology, Department of / Graduate

This thesis deals with questions of the adrenaline centres as the modern product of tourism. The main aim was to open this theme and to resume primary characteristics of the adrenaline centres. The thesis attempts to describe development of adrenaline tourism, to specify the localities, where the adrenaline centres are located and to qualify their influence on regional development. The pozitive effect of this thesis is creation of database of adrenaline centres in Czechia and their primary characteristics, also with the offer of adrenaline activities by the web agencies, that sell the vouchers on these activities. As the example of adrenaline centres was chosen the project of Offpark in Sušice, where the visitors filled in the questionnares. The aim was to find out primary information about the visitors of the adrenaline centres in relation to Offpark. These answers and the information about Offpark minister to brief estimation of the influence of Offpark on regional development on Sušice. Key words: adrenaline centre, adrenaline activities, tourism, Offpark, Sušice

No description available.

published_or_final_version / Physiology / Doctoral / Doctor of Philosophy

published_or_final_version / Physiology / Doctoral / Doctor of Philosophy

No description available.

Naloxone (NX) potentiated epinephrine (EPI) induced submaximal vasoconstriction in canine renal and skeletal muscle arterial segments, yet had no vasoconstrictor action alone. Developed tension generated in-vitro by 4 x 1mm. O.D. rings from 1st degree branches of canine femoral arteries was expressed as % of KCI induced maximum response. NX (10^-5 M) potentiated EPI induced submaximal contractions (34.2%) significantly more than contractions induced by norepinephrine, phenylephrine, lofexidine, ADH, KCI and serotonin (13.8,13.4,4.7,13.5,14.4 and 11.4% respectively). The NX response was unaffected by beta-adrenergic blockade and NX did not reverse an isoproterenol mediated vasodilation. Alphaadrenergic blockade with phentolamine completely eliminated EPI plus NX induced vasoconstriction. After washout, vessels exposed to EPI plus NX relaxed by 50% significantly faster than vessels exposed to EPI alone (18.5 and 27.9 min respectively). EPI induced vasoconstrictions were potentiated by 10^-5 M corticosterone (49.0%) which inhibits extraneuronal catecholamine uptake, but not by 10^-7 M desipramine (1.1%) which inhibits neuronal uptake. EPI induced vasoconstrictions were also potentiated by 10^-4 M pyrogallol (33.0%) which inhibits catechol-o-methyl transferase activity, but not by 10^-5 M pargyline (-1.1%) which inhibits monoamine oxidase activity. The NX effect was endothelium independent. The dose-response of various opioid receptor agonists and antagonists were compared to the NX response. A specific opioid receptor subclass could not be identified as the mediator of the NX effect. The ED_50s for NX (3.7x^-6 M) and (+)NX (8.1x^-7M) indicated a significant stereoselectivity for the (+)enantiomer. A variety of sigma receptor ligands, steroids and steroid metabolites were tested for the ability to augment EPI vasoconstrictions. Several of the opioid, sigma and steroid ligands, all with polycyclic structures, induced responses similarto those of NX. NX exerted its effect independent of traditional opiate receptors and may have influenced the cellular uptake or degradation of EPI. Endogenous compounds with sigma or steroid activity may modulate these processes in-vivo.