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Biomedical subjects

B Bucher

Publications and source records attributed to B Bucher.

At least 55 records · Page 3Linked to original sources
PubMed1992

Prejunctional opioid mu-receptors and adenosine A1-receptors on the sympathetic nerve endings of the rat tail artery interact with the alpha 2-adrenoceptors.

Experiments were designed to study the interaction between prejunctional alpha 2-adrenoceptors and both adenosine and opioid receptors at the postganglionic sympathetic nerve endings innervating the tail artery of the rat. Segments of this vessel were preincubated with [3H]-noradrenaline and then perfused/superfused with [3H]-noradrenaline-free medium. Their perivascular nerves were field stimulated with standard stimulation parameters: 24 pulses at 0.4 Hz, 0.3 ms, 200 mA. In some experiments, the stimulation parameters were adjusted in order to obtain similar reference release values despite the presence of a first release-modulating drug. The adenosine agonist 5'-N-ethylcarboxamidoadenosine (NECA; 0.3-10 mumol/l) and [D-Ala2,MePhe4,Glyol5]enkephalin (DAGO; 0.3-10 mumol/l) depressed the stimulation-evoked overflow of tritium in a concentration dependent manner. The release-inhibiting effect of both NECA and DAGO was enhanced in the presence of the alpha 2-adrenoceptor antagonist rauwolscine (3 mumol/1) while it was attenuated in the presence of the alpha 2-adrenoceptor agonist 5-bromo-6-[2-imidazolin-2yl-amino]-quinoxaline (UK-14,304; 0.1 mumol/l). These changes occurred both at standard and adjusted stimulation parameters. These results demonstrate that the prejunctional adenosine A1- and opioid mu-receptors interact with the prejunctional alpha 2-adrenoceptors. The level at which these interactions take place (receptors themselves or transduction mechanisms) as well as the physiological significance of the phenomenon remain to be determined.

Adenosine↗
PubMed1992

Role of the L-arginine-NO pathway and of cyclic GMP in electrical field-induced noradrenaline release and vasoconstriction in the rat tail artery.

1. The possible roles of the L-arginine-NO pathway and of guanosine 3':5'-cyclic monophosphate (cyclic GMP) in regulating the prejunctional release of noradrenaline and neurogenic vasoconstriction were investigated in the perfused rat tail artery. 2. In the presence of N omega-nitro-L-arginine methyl ester (L-NAME; 30 microM), an inhibitor of NO formation, the vasoconstrictor responses to perivascular nerve stimulation (24 pulses at 0.4 Hz, 0.3 ms, 200 mA) and to exogenous noradrenaline (1 microM) were significantly enhanced, whereas the stimulation-evoked tritium overflow from [3H]-noradrenaline preloaded arteries was not modified. The vasoconstriction enhancing effect of L-NAME was prevented by L-arginine (1 mM) but not D-arginine (1 mM) and was abolished by removal of the endothelium. 3. The NO donor, 3-morpholinosydnonimine-N-ethylcarbamide (SIN-1; 0.1-30 microM), and the cyclic GMP phosphodiesterase inhibitor, zaprinast (0.1-30 microM) both induced a concentration-dependent inhibition of the electrical field stimulation-induced vasoconstriction, while atrial natriuretic peptide (ANP; 100 nM) produced only a slight decrease of the vasoconstrictor response. Methylene blue (3 microM), a known inhibitor of soluble guanylate cyclase increased the electrical field stimulation-induced vasoconstriction. SIN-1 and methylene blue when administered simultaneously, antagonized each others effect. None of the compounds tested (SIN-1, zaprinast, ANP or methylene blue) had any significant effect on the stimulation-evoked [3H]-noradrenaline overflow. 4. 8-Bromo-cyclic GMP, a potent activator of cyclic GMP-dependent protein kinase, markedly and concentration-dependently (3-300 microM) increased [3H]-noradrenaline overflow but decreased field stimulation-induced vasoconstriction. Dibutyryl-cyclic GMP (100 JM), a weak activator of cyclic GMP-dependent protein kinase, affected neither the pre- nor the postjunctional response to electrical field stimulation.5. These data show that an NO-like substance of endothelial origin, derived from L-arginine, attenuates vasoconstriction in the rat tail artery, whether neurally-induced or evoked by exogenous noradrenaline.Since noradrenaline release was unaltered by compounds modifying NO production, this NO-like compound acted through a postjunctional mechanism. The lack of prejunctional effects of both soluble and membrane-associated guanylate cyclase activators, despite a large effect of 8-bromo-cyclic GMP,suggests that endogenous cyclic GMP production, if present in sympathetic nerves, may not be involved in the regulation of noradrenaline release in the rat tail artery.

Animals↗
PubMed1991

Protein kinase C and alpha 2-adrenoceptor-mediated inhibition of noradrenaline release from the rat tail artery.

In isolated rat tail arteries preincubated with [3H]noradrenaline, electrical field stimulation evoked the overflow of tritium. Phorbol 12-myristate 13-acetate (PMA), a protein kinase C (PKC) activating phorbol ester, time-dependently increased the overflow at 1 mumol/L but not at 0.1 mumol/L. In contrast, the overflow was not altered by phorbol 13-acetate (PA, 1 mumol/L), which does not influence the activity of PKC. Polymyxin B (70 mumol/L), an inhibitor of PKC, depressed the overflow when given alone and, in addition, attenuated the effect of PMA, 1 mumol/L. The selective alpha 2-adrenoceptor agonist B-HT 933 depressed the overflow; PMA, 1 mumol/L, did not interfere with the effect of B-HT 933, 10 mumol/L. The results provide evidence for the participation of prejunctionally located PKC in the release of noradrenaline. However, PKC does not seem to be involved in the alpha 2-adrenoceptor-agonist-mediated inhibition of noradrenaline release.

Adrenergic alpha-Agonists↗
PubMed1990

Role of cyclic AMP in the prejunctional alpha 2-adrenoceptor modulation of noradrenaline release from the rat tail artery.

Experiments were designed to evaluate the effect of cyclic AMP on the electrically-induced release of noradrenaline from vascular sympathetic nerve terminals. The possible implication of the inhibition of adenylate cyclase in the negative feed-back control by prejunctional alpha 2-adrenoceptors of neurotransmitter release was also investigated. Rat isolated tail arteries were preincubated with [3H]-noradrenaline; the preparations were subsequently perfused/superfused with [3H )-noradrenaline-free medium and their perivascular nerves were field stimulated with 24 pulses at 0.4 Hz (0.3 ms, 200 mA). 2 compounds known to enhance the intracellular concentration of cyclic AMP, namely the membrane permeant analogue 8-Br-cAMP (10-300 mumol/l) and forskolin (0.3-10 mumol/l), an activator of adenylate cyclase, concentration-dependently enhanced the stimulation-evoked tritium overflow. The 1,9-dideoxy derivative of forskolin, which does not stimulate adenylate cyclase, was ineffective. Exposure to the cyclic AMP phosphodiesterase inhibitor rolipram 30 mumol/l produced a moderate increase (about 20%) in tritium overflow. However, in the presence of rolipram the facilitatory effect of forskolin was significantly more pronounced than in its absence. Whereas 8-Br-cAMP produced a slight concentration-dependent enhancement of the stimulation-induced vasoconstriction, forskolin and rolipram depressed it. The alpha 2-adrenoceptor agonist B-HT 933 (3-30 mumol/l) concentration-dependently inhibited the tritium overflow. The effect of B-HT 933 30 mumol/l was slightly, but significantly reduced in the presence of 8-Br-cAMP 100 and 300 mumol/l, but was not changed in the presence of forskolin 3 mumol/l. The facilitatory effect of rauwolscine 1 mumol/l was enhanced in the presence of 8-Br-cAMP 100 mumol/l. During perfusion with 8-Br-cAMP 100 mumol/l, the current strength and frequency were decreased to 150 mA and 0.2 Hz, respectively in order to obtain similar amounts of tritium overflow to those observed in the absence of the cyclic AMP analogue with the initial stimulation parameters. Under these conditions, the inhibition of the overflow by B-HT 933 30 mumol/l and the facilitation by the alpha 2-adrenoceptor antagonist rauwolscine 1 mumol/l were unaltered as compared to controls under initial stimulation conditions. It is concluded that, in the rat tail artery, the terminals of perivascular sympathetic nerves are endowed with an adenylate cyclase system. Cyclic AMP is able to modulate noradrenaline release, but does not appear to play a role in the initiation of the release process itself. In addition, the results do not support the hypothesis that prejunctional alpha 2-adrenoceptors depress noradrenaline release through the inhibition of adenylate cyclase.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1989

Subsensitivity of presynaptic adenosine A1-receptors in caudal arteries of spontaneously hypertensive rats.

(-)-N6-(R-phenylisopropyl)-adenosine (R-PIA) depressed tritium overflow and vasoconstriction evoked by electrical stimulation to a similar extent in isolated tail arteries of Wistar rats (WR) preincubated with [3H]noradrenaline. The inhibitory effects of adenosine, 5'-N-ethylcarboxamidoadenosine (NECA) and R-PIA were determined on the constrictor responses of tail arteries obtained from WR, as well as spontaneously hypertensive (SHR) and Wistar Kyoto rats (WKY). In WR and WKY, the rank order of agonist potency (R-PIA greater than NECA greater than adenosine) was compatible with the presence of adenosine A1-receptors. Whereas adenosine, NECA and R-PIA were equiactive in WR and WKY, they produced no or only slight changes in SHR. The left renal arteries of some WR were partially occluded to induce hypertension. R-PIA had the same effect in the tail arteries of these animals as in preparations obtained from sham-operated WR. The above results suggest that the subsensitivity of presynaptic A1-receptors in the blood vessels of SHR is genetically determined. This could contribute in vivo to enhanced transmitter release from terminals of perivascular nerves and subsequent increases in vascular resistance.

Adenosine↗
PubMed1988

Further evidence for the existence of a homogenous beta-endorphin-sensitive receptor population in the rat tail artery.

Isolated rat tail arteries were perfused and vasoconstriction was evoked by electrical field stimulation (2 pulses at 1 Hz every 2 min). The vasoconstriction was depressed by DAGO (IC50 = 611 nM) and beta-endorphin (IC50 = 37 nM). Structuraly analogues and shorter fragments of beta-endorphin were also tested. beta-Endorphin and beta-endorphin-(1-26) were about equipotent whereas the beta-endorphin fragments 1-17, 1-16 and 6-31 were inactive. The potencies of beta-endorphin, beta-endorphin-(1-26), -(1-17) and -(1-16) were not changed in the presence of peptidase inhibitors. Structural analogues such as [D-Ala2]beta-endorphin or [Leu5]beta-endorphin had a somewhat lower potency than beta-endorphin itself. Naloxone 30 nM antagonized the effects of DAGO and beta-endorphin to a similar extent with dissociation constants 3.8 and 3.7 nM, respectively for the antagonist against the agonists. The results support the existence in the rat tail artery of a homogenous population of beta-endorphin-sensitive receptors which may belong to the epsilon-type.

Animals↗
PubMed1987

Adrenomedullary and beta-adrenergic participation in enhanced sympathetic pressor responses of spontaneously hypertensive rats.

The beta-adrenergic and adrenomedullary components of pressor responses to sympathetic nerve stimulation were studied in spontaneously hypertensive rats (SHR) and normotensive Wistar Kyoto rats (WKY). The effects of electrical stimulation of the entire spinal cord of pithed rats pretreated with tubocurarine and atropine were studied on systolic blood pressure, heart rate and plasma cyclic AMP levels. The heart rate increase upon low frequency stimulation (1 Hz) and the blood pressure elevation upon stimulation at higher frequencies (3 and 5 Hz) were higher in SHR than in WKY whereas the increase in circulating cyclic AMP level was not different in the two strains. Pretreatment with propranolol (2.5 mg X kg-1) further enhanced the pressor responses in SHR but not in WKY, although it inhibited the heart rate acceleration and decreased the circulating level of cyclic AMP similarly in the two strains. After acute adrenalectomy, the elevations of blood pressure and circulating cyclic AMP levels were reduced to an identical level in SHR and WKY. These results show that the marked enhancement of the pressor response observed in SHR upon stimulation of the entire sympathetic outflow is mostly of adrenomedullary origin and includes a hypotensive component due to beta-adrenoceptor stimulation which is not present in WKY.

Adrenal Medulla↗
PubMed1987

Beta-endorphin-sensitive opioid receptors in the rat tail artery.

Isolated tail arteries of rats were perfused and field-stimulated every 2 min with 2 pulses at 1 Hz. Different opioid peptides depressed the contractile responses to stimulation; their concentration-response curves showed a maximum at about 40% inhibition. The rank order of potency of the peptides was beta-endorphin (IC50 = 97 nmol/l) approximately equal to BAM-22P greater than FK-33824 greater than DAGO greater than [D-Ala2,D-Leu5]-enkephalin greater than or equal to metorphamide greater than dynorphin A-(1-13) approximately equal to [Met5]enkephalin. All these substances have in common a certain activity at opioid mu-receptors, although the enkephalins are preferential delta-, and the dynorphins preferential kappa-agonists. However, the selective delta-agonist [D-Pen2,L-Pen5]enkephalin was ineffective at up to 10 mumol/l, and the kappa-agonists ethylketocyclazocine and U-50488 acted only at concentrations higher than 3 mumol/l. Whereas the effects of beta-endorphin, DAGO and [D-Ala2,D-Leu5]enkephalin could be reduced by the mu-preferential antagonist naloxone, the effects of ethylketocyclazocine and U-50488 were not changed. The delta-selective antagonist ICI 174864 did not influence the action of [D-Ala2,D-Leu5]enkephalin. Naloxone in a concentration (1 mumol/l) which nearly abolished the effect of DAGO 3 mumol/l, slightly enhanced responses to stimulation. Neither beta-endorphin nor DAGO influenced vasoconstriction evoked by the application of noradrenaline or adenosine triphosphate; U-50488 reduced it. In arteries preincubated with [3H]noradrenaline DAGO depressed, whereas naloxone enhanced the tritium overflow and vasoconstriction evoked by field stimulation (0.4 Hz, 24 pulses every 14 min). In addition, naloxone antagonized the effect of DAGO.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Plasma concentration and vascular effect of beta-endorphin in spontaneously hypertensive and Wistar Kyoto rats.

In order to find out whether beta-endorphin (beta-E) is involved in the development of hypertension, we performed two series of experiments. Firstly, spontaneously hypertensive rats (SHR) and their normotensive Wistar Kyoto controls (WKY) were submitted to ether stress. Plasma concentrations of beta-endorphin-like immunoreactivity (beta-EI), adrenocorticotropin (ACTH) and alpha-melanotropin (alpha-MSH) were measured by radioimmunoassay. The basal concentration of beta-EI was similar in WKY and SHR, whereas WKY had higher levels of ACTH and lower levels of alpha-MSH than SHR. In both strains acute stress enhanced the plasma concentration of beta-EI to the same extent and with a similar time-course. The increase of plasma beta-EI coincided with a rise in ACTH but not alpha-MSH. Gel chromatography of beta-EI revealed that plasma extracts contain similar amounts of beta-lipotropin- (beta-LPH) and beta-E-sized immunoreactive components, and that acute stress elevated both forms of beta-EI. Secondly, isolated tail arteries of SHR and WKY were perfused and field stimulated with two pulses at 1 Hz. beta-E depressed stimulation-evoked vasoconstriction with the same potency in both strains. Thus, basal and stress-induced levels of beta-EI did not differ in SHR and WKY. Moreover, in the tail artery of both strains the sensitivity of presynaptic opioid receptors towards beta-E was almost identical. If the beta-E sensitivity of these receptors in other arteries of WKY and SHR is also similar a major role of the circulating peptide in the development of hypertension is rather unlikely.

Adrenocorticotropic Hormone↗
PubMed1986

Generalization of a sign language rehearsal strategy in mentally retarded and hearing deficient children.

Memory deficits are common in mentally retarded individuals who lack verbal skills. Training in manual signing may be of value. In this study we trained a sign language rehearsal strategy so that the strategy would be used with no instructions to perform it; and assessed whether the strategy would transfer across tasks, and how to train for transfer. Subjects were five essentially nonverbal severely mentally retarded children and three essentially nonverbal deaf children. Each was trained to use a sign-rehearsal strategy in one of two memory tasks. Use of the strategy showed marked increases when children were instructed to rehearse, but showed less change when no instructions were given. Generalization to uninstructed trials was then achieved by gradually delaying the instructions. After this training, two of three children trained in a more complex task transferred uninstructed sign-rehearsal to a less complex task, but children trained in the simpler task did not generalize to the complex task.

Adolescent↗
PubMed1984

Age-related changes of in vivo beta-adrenergic responsiveness in normotensive and spontaneously hypertensive rats.

The variations of plasma cyclic AMP concentration caused by propranolol and isoproterenol were studied in order to investigate endogenous stimulation and responsiveness of the beta-adrenoceptor-cyclic AMP system in vivo, in 7 and 18 week old unanaesthetized male SHR and WKY. In both age groups, the basal cyclic AMP level was higher in SHR than in controls but was significantly reduced to a comparable value in the two strains after intraperitoneal injection of 2.5 mg X kg-1 propranolol, a dose which markedly depressed or even abolished the effect of isoproterenol. Cumulative dose-response curves of plasma cyclic AMP concentration obtained in another group of rats after successive subcutaneous injections of isoproterenol showed that the ED50 value of this drug was higher in SHR than in WKY and increased in a parallel manner in the two strains between 7 and 18 weeks of age (respectively from 0.21 +/- 0.01 to 0.34 +/- 0.02 mumol X kg-1 in WKY and from 0.32 +/- 0.02 to 0.52 +/- 0.03 mumol X kg-1 in SHR). At the same time blood pressure increased much less markedly in WKY (from 115 +/- 4 to 119 +/- 2 mm Hg) than in SHR (from 134 +/- 3 to 179 +/- 3 mm Hg). Altogether these results show that endogenous beta-adrenergic stimulation of the cyclic AMP system was higher in SHR of both ages in spite of a diminished responsiveness of this system to exogenous isoproterenol.

Aging↗
PubMed1984

Smooth muscle cell hypertrophy and hyperplasia in the thoracic aorta of spontaneously hypertensive rats.

Changes in the smooth muscle cell compartment (SMCC) of the media layer of the aorta were studied in spontaneously hypertensive (SHR) and in normotensive rats (WKY) of both sexes between 3 to 18 weeks of age. Up to 7 weeks of age, development of the SMCC occurred in males and females of the two strains both through a massive increase in cell number and in cell size. In SHR after 7 weeks of age, the development of the SMCC was due to a marked increase in cell size together with an increase in cell number. In contrast during the same period, the development of the SMCC in WKY was associated almost exclusively with an increase in cell size. It is concluded that the presence of a greater number of larger smooth muscle cells contributes to the hypertrophy of the arterial wall of hypertensive animals.

Aging↗
PubMed1984

Prompting and stimulus shaping procedures for teaching visual-motor skills to retarded children.

Stimulus shaping appears to be a highly successful way to teach discrimination skills. In stimulus shaping, the topographical configuration of the stimuli is gradually changed over trials so that discrimination is at first easy, and then gradually more difficult. Stimulus shaping procedures might also be effective for training visual-motor tasks. Two experiments were conducted to assess the relative effectiveness of stimulus shaping and "traditional" prompting procedures. Pegboard skills were trained in Experiment 1. In Experiment 2 a self-care skill was trained, in which children learned to hang a toothbrush or a washcloth on a specific hook. Six low-functioning retarded children were studied in each experiment, using a within-subject alternating treatments design. Each participant received concurrent training on two related tasks, using stimulus shaping for one and a standard prompting procedure for the other. Training with the stimulus shaping procedure required less training time to criterion, always resulted in fewer errors, always required fewer and less intrusive therapist's prompts, and always resulted in greater density of reinforcement. These results demonstrate the value of stimulus shaping strategies for training visual-motor skills.

Behavior Therapy↗