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Biomedical subjects

K Magyar

Publications and source records attributed to K Magyar.

At least 109 records · Page 6Linked to original sources
PubMed1986

Feedback control of arterial smooth muscle tone: the role of prostacyclin.

Indomethacin potentiated noradrenaline (NA)-induced contractions of rabbit isolated mesenteric arteries. Mechanical removal of the endothelium did not influence its potentiating effect. Prostacyclin (PGI2) synthesis was stimulated by NA (0.1-1.0 mumol l-1) and inhibited by indomethacin in a concentration-dependent manner. There was a positive correlation between the indomethacin-induced inhibition of PGI2 formation and the indomethacin-evoked potentiation of contractile responses to NA. These results suggest that endogenous PGI2 plays a part in the feedback control of vascular smooth muscle tone.

6-Ketoprostaglandin F1 alpha↗
PubMed1986

[3H]noradrenaline-releasing action of vinpocetine in the isolated main pulmonary artery of the rabbit.

Vinpocetine (10(-6)-3 X 10(-5) M) increased both the resting and the nerve stimulation-evoked release of [3H]noradrenaline from the isolated main pulmonary artery of the rabbit in the presence of uptake blockers (cocaine, 3 X 10(-5) M; corticosterone, 5 X 10(-5) M), and inhibited the nerve stimulation-evoked postsynaptic response. The resting transmitter releasing action of vinpocetine increased in the absence of cocaine. Exogenously applied (-)noradrenaline [(-)NA] (10(-6) M) or clonidine (10(-6) M) inhibited the vinpocetine (3 X 10(-5) M)-potentiated [3H]NA release and contracted the circular muscle. The clonidine-induced contraction was abolished by 10(-7) M prazosin. The inhibitory action of (-)-NA on vinpocetine-potentiated [3H]NA release was partly antagonized by 3 X 10(-7) M yohimbine, a preferential alpha 2-adrenoceptor blocker. In Ca-free Krebs solution containing 1 mM EGTA the neurotransmitter releasing action of vinpocetine was abolished, however, its stimulating action on the resting [3H]NA outflow was not changed. In Na-pump-inhibited arteries (K-free solution), where both the resting and the nerve stimulation-evoked release of neurotransmitter had already been increased, vinpocetine further enhanced the nerve stimulation-evoked release of [3H]NA. It is concluded that vinpocetine may have alpha 2- and alpha 1-adrenoceptor blocking action, as well as a tyramine-like effect. The presynaptic neurotransmitter releasing action of vinpocetine is presumably the consequence of its inhibitory action on the Ca-pump which is suggested by the finding that in K-free solution vinpocetine was able to enhance further the release of neurotransmitter.

Animals↗
PubMed1986

Ouabain-evoked [3H]noradrenaline release from the rabbit pulmonary artery in calcium-free solution.

[3H]noradrenaline ([3H]NA) release from the isolated main pulmonary artery of the rabbit has been measured in the presence of neuronal (cocaine, 3 X 10(-5) M) and extraneuronal (corticosterone, 5 X 10(-5) M) uptake blockers. 10(-4) M ouabain significantly increased the [3H]NA release in normal external ionic environments after an initial delay (20-30 min). Excess K (23.6 mM) failed to affect the resting [3H]NA outflow, significantly inhibited the ouabain-stimulated [3H]NA release and shortened the initial delay by about 10-20 min. Higher concentration of K (47 X 2 mM) enhanced the outflow of [3H]NA. In the absence of external Ca and in the presence of 1 mM EGTA, 23.6 mM-K failed to exert an inhibitory action on ouabain evoked transmitter release. Higher concentrations of K, however, significantly inhibited the [3H]NA-releasing effect of ouabain without changing the resting outflow of labelled neurotransmitter. The initial delay of ouabain-evoked [3H]NA release was shortened by increasing the concentration of K. Total substitution of external Na by K (143.3 mM) increased the [3H]NA release in the absence of external Ca. After the Na gradient was re-established in Ca-free solution the release of [3H]NA was terminated. Under these conditions the NA-releasing action of ouabain was dependent on the preceding perfusing period in Na-free solution, being smaller if longer exposure time was used. When external Na was substituted by Li (137.4 mM) in Ca-free solution the [3H]NA release was dramatically increased. After Na readmission ouabain was ineffective in producing transmitter release. It is suggested that in the main pulmonary artery of the rabbit, when the electrochemical gradient of Ca is reversed, ouabain is effective in producing transmitter release if the internally stored Ca has not been completely lost. Since in Ca-free solution the ouabain-evoked [3H]NA release can be inhibited by external K it seems that the transmitter release observed is due to a Na-dependent release of intracellular Ca rather than the penetration of ouabain into the cell followed by direct inhibition of the active transport of internal store membranes.

Animals↗
PubMed1986

Irregular chronic stress related selective presynaptic adaptation of dopaminergic system in rat striatum: effects of (-)deprenyl and amitriptyline.

Rats were exposed to irregular chronic stress (IRCS, an animal model of depression). Changes in dopamine and serotonin utilization by striata and hippocampi were measured. IRCS did not influence serotonin uptake, serotonin, dopamine, 5-hydroxyindolacetic acid and homovanillic acid levels, while it decreased 3,4-dihydroxyphenylacetic acid level and dopamine uptake. This would reflect selective presynaptic adaptation to IRCS. Neither (-)deprenyl (21 X 0.25 mg/kg, s.c.), nor amitriptyline (21 X X 15 mg/kg, i.p.) could prevent the effects of IRCS.

Adaptation, Physiological↗
PubMed1985

Evidence for the role of cAMP-dependent protein kinase in the down-regulation of hypothalamic HD: reversal of cAMP-(ATP) induced inhibition of HD activity by the 'Walsh' inhibitor of cAMP-dependent protein kinase and by cyclic GMP.

Under the total blockade of PDE1 and the presence of endogeneous ATP and MgCl2, the inhibitory effect of cAMP on HD activity could be demonstrated as low as 8.7 X 10(-8) M concentration in a 20,000 g supernatant of a sustained homogenate of rat hypothalamus. A total reverse of this action and also a partial release of the cAMP-induced inhibition of HD, occurred at higher concentrations of cAMP, and ATP could be achieved by an endogeneous inhibitor of cAMP-dependent protein kinase or by cyclic GMP. The reversal of cAMP action by PKI seems to serve a strong evidence for the role of cAMP-dependent protein kinase (EC 2.7.37: ATP-protein phosphotransferase) in this action and emphasized the involvement of a direct or an indirect phosphorylation in the regulation of HD activity. The stimulatory effect of cyclic GMP on cAMP-induced inhibition of HD or its 'direct' effect on histamine formation is asserted, probably through the activation of PDE, or through independent stimulatory machinery, coupled to the cyclic GMP system.

Adenosine Triphosphate↗
PubMed1985

Species dependent relaxation of intrapulmonary arteries (IPA) of rabbits, dogs and humans by prostacyclin.

Helically cut strips of successive IPA segments of rabbits, dogs and human patients were set up for isometric recording in vitro. High tone was produced by norepinephrine (NE, 3 microM). This tone was markedly reduced by prostacyclin (PGI2) in the secondary, tertiary and quaternary branches of human and canine pulmonary trunk. The IC50 values for PGI2 ranged from 22 to 503 nM, the human vessels being more sensitive to prostacyclin than canine IPA. Under these conditions, the primary and secondary branches of the rabbit pulmonary trunk were not relaxed by PGI2. The contractile potency of NE was determined in each pulmonary vessel studied. The secondary segments of rabbit IPA were about ten times as sensitive to NE (EC50 for NE: 38 +/- 7 nM) as compared to the secondary IPA from dogs and humans (EC50 values: 370 +/- 84 and 440 +/- 50, respectively). When high tone was induced by equieffective contractile concentrations of NE (3 microM for canine and human IPA and 0.3 microM for rabbit vessels), PGI2 was still less effective (P less than 0.01) in relaxing secondary IPA of rabbits (IC25: 220 +/- 55) than the corresponding segments of dogs and humans (IC25: 51 +/- 12 and 17 +/- 4, respectively). The difference between canine and human vessels was also significant (P less than 0.02). These results indicate that there is an interspecies difference in the sensitivity of IPA to NE and PGI2.

Animals↗
PubMed1985

Presynaptic autoinhibition during rest and sodium-pump inhibition in isolated rat portal vein preparation.

In the presence of cocaine and corticosterone low-frequency (2 Hz) nerve stimulation evoked release of [3H]noradrenaline measured from isolated rat portal vein preparation. In normal Krebs solution exogenously applied l-noradrenaline (3 X 10(-8)-10(-6) M) significantly reduced the nerve-evoked [3H]noradrenaline release. The IC50 value of L-noradrenaline proved to be 1.8 X 10(-7) M. Yohimbine (3 X 10(-7) M) maximally blocked the alpha 2-adrenoceptors and enhanced nerve-evoked [3H]noradrenaline release. In the presence of 5.9 mM external K+, ouabain up to 10(-4) M did not affect either the resting or the stimulation-evoked release of radioactivity from tissues. In the absence of external K+ both the resting and the nerve-evoked release of [3H]noradrenaline increased markedly. When K+ was readmitted to preparations which had been kept in K+-free solution both the resting and the stimulation-evoked [3H]noradrenaline release were greatly reduced temporarily. In K+-free solution L-noradrenaline (10(-6) M) and yohimbine (3 X 10(-7) M) failed to significantly alter the nerve-evoked release. However, 3 X 10(-6) M yohimbine in K+-free solution significantly increased the stimulation-evoked release of [3H]noradrenaline. It is concluded that presynaptic alpha 2-adrenoceptor-mediated "negative feed-back" is present in rat portal vein preparations which can be inhibited by the preferential alpha 2-adrenoceptor blocker, yohimbine. However, if the Na+-pump is inhibited (which by itself enhanced the transmitter release), presynaptic autoinhibition is more pronounced, since a high concentration of yohimbine is required to block it.

Animals↗
PubMed1985

Transient inhibition of the muscarinic actions of carbachol during reactivation of the electrogenic sodium pump in guinea pig taenia caeci smooth muscle.

In guinea pig taenia caeci smooth muscle the muscarinic receptor stimulant carbachol evoked depolarization and contraction, which was followed by hyperpolarization and relaxation on its removal. Both the hyperpolarization and relaxation were inhibited by removal of K+ from the external medium. During Na+-pump blockade (K+-free solution) the depolarizing and contracting actions of carbachol decreased. When the Na+ pump was switched on again by readmission of 5.9 mmol/L K+ to K+-depleted and Na+-enriched preparations, electrogenic hyperpolarization and relaxation developed. During this period carbachol failed to produce depolarization and contraction.

Animals↗
PubMed1984

Differential contractile responsiveness of isolated rabbit arteries from different vascular beds to cyclooxygenase inhibitors and PGI2.

The actions of three, structurally unrelated cyclooxygenase inhibitors and PGI2 on the contractile responses to electrical stimulation and to noradrenaline of strips of rabbit coeliac, ear, pulmonary, carotid, femoral arteries and the aorta were studied. Indomethacin (3 mumol/l), suprofen (0.8 mumol/l) and meclofenamic acid (0.2 mumol/l) potentiated the adrenergically induced contractions of coeliac arteries by 126-165%. The contractile responses of ear arteries were increased by these three substances by 87-91%, and the responses of pulmonary arteries by 26-33%. All of these changes were statistically significant. Prostacyclin produced a dose-related inhibition of the stimulation-induced contractions of the coeliac, ear and pulmonary arteries; its IC50 values were 10.4, 212 and 433 nmol/l, respectively. In contrast to effects in the above arteries, the evoked contractions of aortic and carotid strips were not affected by any of the prostaglandin synthesis inhibitors used; the responses of femoral vessels were reduced by all of the inhibitors (by 13-23%; P less than 0.05). Low concentrations of PGI2 did not affect the evoked contractions of aortic, carotid and femoral strips whereas higher concentrations increased baseline tone and potentiated contractions. The results indicate that there are considerable difference in the sensitivities of the arteries from different vascular beds to inhibitors of cyclooxygenase and to prostacyclin.

Animals↗
PubMed1984

Regulation of histidine decarboxylase activity in rat hypothalamus in vitro by ATP and cyclic AMP: enzyme inactivation under phosphorylating conditions.

In vitro, hypothalamic HD1 from rat, could strikingly be inhibited by ATP and cyclic AMP. The enzyme inhibition is partially dependent upon Mg2+ and the circumstances favourable for a cAMP-dependent phosphorylation. An almost complete inhibition could be achieved by incubating the homogenate of the hypothalamus under phosphorylating conditions (ATP, cAMP, Mg2+ and IBMX) in the presence of a cAMP-dependent protein kinase (obtained from bovine thymus). Cyclic nucleotides and ATP alone elicit only moderate inhibitions on the hypothalamic HD activity. Neither ATP, nor cAMP, added alone or in combinations, alter the total brain or the hypothalamic HNMT from guinea-pigs or rats in concentrations up to 10(-3) M. Results suggest that hypothalamic HD is regulated through a cAMP-dependent process, probable a direct phosphorylation, via a cAMP-dependent protein kinase.

Adenosine Triphosphate↗
PubMed1984

Regulatory influence of histamine receptor activation and inhibition on the synthesis and level of hypothalamic histamine.

The blockade of histamine receptors by repeated i.p. administration of 10-20 mg/kg of chloropyramine and tripelennamine, the potent H1-receptor antagonists, or by the i.c.v. administration of 2 mg/kg of metiamide and cimetidine, the highly selective H2-receptor antagonists, led to significant enhancement in the hypothalamic HD2(L-histidine carboxylase; EC 4.1.1.22.) activity and the histamine content; whereas the activation of the histamine H1-receptor by 4 mg/kg i.e.v. doses of 2-pyridylethylamine, the specific histamine H1 agonist, resulted in significant diminution in both the synthesis and level of this amine. These compounds either do not influence the hypothalamic HD in vitro or cause opposite effects in relatively high concentrations. After repeated administration of either agonists or antagonists, no significant alteration have been observed in the hypothalamic HNMT (histamine-N-methyl-transferase; EC 2.1.1.8.) activity. There were, however, two exceptions: 2 mg/kg i.c.v. doses of 2-methylhistamine and 4-methylhistamine produced remarkable inhibitions in the hypothalamic HNMT activity. These effects do not seem to correspond to the agonistic character of the compounds, but mask the indirect actions and create difficulties in the discovery of regulatory events. The regulatory influence which suppresses or stimulates the basal activity of HD under the activation or the inhibition of the functional state of histamine receptor, is assumed to be mediated through the cyclic AMP system.

Animals↗
PubMed1984

The inhibitory action of PGF2 alpha on release of [3H]noradrenaline enhanced by alpha 2-adrenoceptor blockade, sodium-pump inhibition and 4-aminopyridine in the main pulmonary artery of the rabbit.

Large concentrations of prostaglandin PGF2 alpha inhibited the stimulation (2 Hz) evoked release of [3H]noradrenaline from the isolated main pulmonary artery of the rabbit (the inhibition caused by 3 X 10(-5) M PGF2 alpha was 62%). Furthermore, PGF2 alpha inhibited the release evoked by stimulation when it was enhanced by different procedures. During blockade of presynaptic alpha 2-adrenoceptors by 3 X 10(-7) M yohimbine, which by itself enhanced the overflow of [3H]NA in response to stimulation, the inhibitory action of PGF2 alpha was more pronounced (78.2%). In tissue in which the Na+-pump was inhibited (K+-free treatment) where the overflow of 3H was markedly increased, PGF2 alpha exerted nearly equal inhibition of transmitter release to that observed in control experiments (64.3%). The inhibitory effect of PGF2 alpha on the stimulation-evoked release of [3H]NA was less pronounced (32.1%) in the presence of 10(-4) M 4-aminopyridine (a blocker of K+-channels).

4-Aminopyridine↗
PubMed1984

Effect of potassium on the release of [3H]noradrenaline from rabbit and human pulmonary artery.

The release of [3H]noradrenaline ( [3H]NA) from rabbit and human isolated pulmonary artery has been measured. Removal of external potassium ions enhanced both the resting and stimulated release of [3H]NA from the strips. On adding K+ to tissues which had been suspended in K+-free Krebs solution, the release of [3H]NA was reduced in both stimulated and unstimulated tissues. Selective inhibition of presynaptic alpha 2-adrenoceptors by yohimbine significantly potentiated the release of [3H]NA evoked by stimulation in K+-free solution. The presynaptic inhibitory effect of NA was much less pronounced when the release was enhanced by the removal of external K+. Since the activity of NA, K-ATPase may be affected by removing K+ or by adding it to tissue previously kept in K+-free solution, the results may indicate involvement of the sodium pump in NA release.

Animals↗
PubMed1984

[3H]noradrenaline release evoked by selegiline ((-)-deprenyl) in the isolated main pulmonary artery of the rabbit.

High concentrations of selegiline[-)-deprenyl) (greater than 10(-5) M) enhanced the nerve stimulation (2 Hz)-evoked release of [3H]noradrenaline from the isolated main pulmonary artery of the rabbit. This facilitation of stimulation-evoked [3H]noradrenaline release by selegiline was reduced by exogenous (-)-noradrenaline, an agonist of presynaptic alpha 2-adrenoceptors. This inhibitory action of (-)-noradrenaline was partly antagonized by yohimbine, a selective alpha 2-adrenoceptor blocker. When the stimulation-evoked [3H]noradrenaline release had already been increased by inhibition of Na+-pump (K+-free solution), selegiline further enhanced the nerve-evoked release of labelled neurotransmitter.

Animals↗
PubMed1984

Spontaneous [3H]noradrenaline release from the main pulmonary artery of the rabbit induced by sodium-pump inhibition.

Inhibition of Na pump either by ouabain (10(-4) M) or by K removal increased the [3H]noradrenaline [( 3H]NA) release from the isolated main pulmonary artery of the rabbit in the presence of neuronal (cocaine, 3 X 10(-5) M) and extraneuronal (corticosterone, 5 X 10(-5) M) uptake blockers. The ouabain-evoked [3H]NA release began after a delay of about 30 min and peaked after 66 min of ouabain application. Both times were shortened by omission of K from the external medium. About 90% of ouabain-evoked [3H]NA release proved to be external Ca concentration ([Ca]o) dependent and the peak effect was delayed by about 80 min in Ca-free (+ 1 mM EGTA) solution. In the presence of external Ca (2.5 mM) the [3H]NA-releasing effect of 'K-free' treatment was much less pronounced than that of 10(-4) M ouabain, the initial delay in transmitter release was shorter (10-15 min) and the peak effect developed earlier (at 42 min). On readmission of K the [3H]NA release recovered quickly to the original value. Ca removal did not antagonize the transmitter release observed in K-free solution, but the peak release was delayed by about 90 min. A low concentration of ouabain (10(-5) M) failed to produce transmitter release in the presence of normal external K, but markedly increased the release in K-free solution. The release was much bigger than the sum of their separate effects, and the rate of rise was faster than when 10(-4) M ouabain was applied in normal solution. Excess Ca (7.5; 15 mM) inhibited the [3H]NA release observed in K-free solution. 7.5 mM-Ca also delayed the transmitter-releasing action of 10(-4) M ouabain, an effect antagonized by omission of K from the external medium. The mitochondrial uncoupler carbonyl cyanide m-chlorophenylhydrazone (CCCP, 10(-5) M) significantly increased the [3H]NA release in Ca-free, 1 mM EGTA-containing solution, and enhanced the effects of ouabain (10(-4) M). The Ca ionophore A23187 (10(-5) M) also significantly increased the [3H]NA release in the absence of external Ca and in the presence of 1 mM EGTA. Again, in the presence of A23187 the effects of 10(-4) M ouabain in releasing neurotransmitter were enhanced. When CCCP and A23187 were applied together in Ca-free, EGTA solution the [3H]NA releasing action of ouabain was still apparent. Veratridine (10(-4) M) enhanced the transmitter release in the absence of external Ca in a tetrodotoxin (TTX)-sensitive manner.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1984

Measurement of the disaggregating effect of prostacyclin (PGI2) in anaesthetized dogs.

The disaggregating effect of PGI2 was measured in a modified in vivo model first described by Hornstra (5). The arterial blood of mongrel dogs was directed through an extracorporeal filter by a roller pump, and the pressure before the filter was measured. The filter becomes spontaneously occluded within a few minutes, and as a results the pressure before the filter increases continuously. PGI2 administered before the filter or intravenously produced dose-related reduction in filtration pressure. This simple technique seems to be usefull for determining the dis aggregatory effects of prostacyclin and other substances.

Animals↗
PubMed1984

Effects of cyclooxygenase inhibitors and PGI2 on the adrenergic contractions of isolated rabbit arteries.

The effect of three cyclooxygenase inhibitors (indomethacin, suprofen, meclofenamic acid) and PGI2 on the contractile responses to noradrenaline (NA) and to nerve stimulation (TNS) of strips of rabbit coeliac-, pulmonary-, ear-, carotid-, femoral arteries and the aorta were studied. The equipotent concentration (0.1 X EC50) of NA were calculated from dose-response curves. The stimulation parameters (Hz, duration) varied according to the responsiveness of the tissue. Both NA and TNS caused 7-23% of maximum response. In the presence of cyclooxygenase inhibitors (COI's) NA and TNS produced significantly greater proportion (15-30%) of maximum contraction in coeliac-, ear-, and pulmonary arteries. Contractions of the other 3 vessels were not influenced by COI's. The inhibitory potency of PGI2 was determined on contractions produced by equipotent concentration (EC50) of NA. PGI2 was highly effective in coeliac arteries, it was less potent in pulmonary- and ear arteries and had no effect on the responses of the other vessels.

Animals↗