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Biomedical subjects

E Muscholl

Publications and source records attributed to E Muscholl.

At least 37 records · Page 2Linked to original sources
PubMed1983

Uptake of [3H]dopamine into dopaminergic and noradrenergic neurones of the isolated neurointermediate lobe of the rat hypophysis. Effects of desipramine and nomifensine.

The isolated neurointermediate lobe (NIL) of the rat hypophysis accumulates [3H]dopamine from the incubation medium. Column chromatographic analysis showed that 92% of the tissue radioactivity was contained in the catecholamine fraction. [3H]Dopamine represented 70% and [3H]noradrenaline 30% of the [3H]catecholamines. Desipramine (1 microM) prevented the formation of [3H]noradrenaline without affecting the storage of [3H]dopamine. Nomifensine (10 microM) blocked the storage of [3H]dopamine and [3H]noradrenaline. Thus, in the NIL, [3H]dopamine is taken up into dopaminergic and noradrenergic neurones. In the latter, [3H]dopamine is converted to [3H]noradrenaline, indicating a significant dopamine beta-hydroxylase activity in the NIL tissue. A selective labeling of the dopamine stores with [3H]dopamine can be achieved in the presence of desipramine.

Animals↗
PubMed1983

The determination of presynaptic pA2 values of yohimbine and phentolamine on the perfused rat heart under conditions of negligible autoinhibition.

1 Rat isolated perfused hearts with the right sympathetic nerves attached were loaded with [3H]-(-)-noradrenaline. The nerves were stimulated with up to 40 trains of 10 pulses every min at 1 Hz, and the evoked increases of [3H-]noradrenaline overflow into the perfusate, of right atrial tension development and ventricular beating frequency were measured. 2 Oxymetazoline inhibited the evoked transmitter overflow (IC50: 10 nM) and decreased the postsynaptic responses in a concentration-dependent manner. It behaved as a full against in abolishing the evoked transmitter overflow. 3 Yohimbine up to 1 microM neither enhanced the evoked [3H]-noradrenaline overflow nor the postsynaptic parameters. Phentolamine (1 microM) caused a transient, minor (less than 30%) increase in [3H]-noradrenaline overflow. 4 Yohimbine (0.03-1.0 microM) and phentolamine (0.1-5.0 microM) shifted to the right the concentration-response curve of oxymetazoline for the inhibition of [3H]-noradrenaline overflow in response to nerve stimulation without depressing the maxima. The pA2 values were 7.82 and 7.52, respectively. 5 Yohimbine (0.1 microM) also antagonized the decrease induced by oxymetazoline in the postsynaptic responses to nerve stimulation. 6 The results confirm the existence of presynaptic inhibitory alpha 2-adrenoceptors at the adrenergic nerve fibres of the rat heart in vitro. Under the stimulation and perfusion conditions selected, the released endogenous transmitter apparently does not activate a negative feedback mechanism, thus permitting the determination of pA2 values.

Animals↗
PubMed1982

Isoprenaline and forskolin increase evoked vasopressin release from rat pituitary.

Isolated neurointermediate lobes of rat pituitaries were incubated in Krebs solution. The vasopressin release evoked by electrical stimulation (0.2 ms, 80 V, 15 Hz, 10 s trains at 10 s intervals for a total of 10 min) was completely inhibited by tetrodotoxin. Isoprenaline increased the evoked vasopressin release to a maximum of 60% (EC50 10 nM) and this effect was antagonized surmountably by propranolol. Forskolin increased the vasopressin release by 98%. These results suggest the presence within the neurohypophysis of a beta-adrenoceptor-linked adenylate cyclase facilitating vasopressin secretion.

Animals↗
PubMed1982

Sympathetic Nerve Stimulation on the perfused rat heart. Affinities of N-methylatropine and pirenzepine at pre- and postsynaptic muscarine receptors.

Rat isolated hearts with the sympathetic nerves attached were perfused with (-)-3H-noradrenaline in order to label the storage vesicles of the adrenergic nerves. Release was induced either by electrical stimulation of the nerves (3 Hz, 1 min) or by perfusion with high K+ solution (54 mM). The overflow of 3H-noradrenaline and its metabolites was determined by liquid scintillation counting after separation of the compounds by column chromatography. The experimental conditions ensured a minor contribution of 3H-metabolites to the evoked total tritium overflow. The release of 3H-noradrenaline evoked by nerve stimulation or high K+ solution was decreased in the presence of the muscarinic agonist, methacholine, N-methylatropine reversed the inhibition completely. Thus, the rat heart contains inhibitory muscarine receptors modulating noradrenaline release from adrenergic nerve fibres. In order to compare the presynaptic muscarine receptors with postsynaptic muscarine receptors in one and the same organ, the pA2 values of N-methylatropine and pirenzepine at both of these sites were measured. The antagonism of methacholine-induced inhibition of 3H-noradrenaline overflow was determined as the presynaptic parameter. pA2 values of 9.61 for N-methylatropine and 6.63 for pirenzepine were found. The methacholine-induced inhibition of the atrial tension development of isolated left rat atria paced at 2Hz was measured as a postsynaptic parameter. pA2 values of 9.90 for N-methylatropine and 6.69 for pirenzepine were found. The postsynaptic pA2 values did not differ from the presynaptic affinity constants indicating that neither substance revealed differences in structure between neuronal and myocardial muscarine receptors in the rat heart.

Animals↗
PubMed1982

The effect of physostigmine on the vagally induced muscarinic inhibition of noradrenaline release from the isolated perfused rabbit atria.

1. Presynaptic cholinergic-adrenergic interactions were studied on isolated perfused rabbit atria with the extrinsic right vagus and sympathetic innervation intact. The transmitter stores were labelled with 14C-choline and 3H-noradrenaline. The radioactive compounds were separated on columns and determined by scintillation spectrometry. The stimulation-evoked overflow of both transmitters was calcium-dependent and abolished by tetrodotoxin. 2. Methacholine caused a concentration-dependent decrease of atrial tension development and 3H-noradrenaline overflow evoked by 3 Hz sympathetic stimulation. Vagus nerve stimulation (1-20 Hz), although nearly abolishing tension development at 20 Hz, decreased evoked 3H-noradrenaline overflow by not more than 18%. 3. Physostigmine decreased atrial cholinesterase activity by 80% and increased the fraction of stimulation-evoked unhydrolyzed 14C-acetylcholine in the persufates from 58 to 86%. However, the inhibition by vagus stimulation (1-10 Hz) of evoked 3H-noradrenaline overflow was smaller than in the absence of the drug. This was closely related to a decrease in acetylcholine overflow. Yet for a give fractional rate of acetylcholine release the muscarinic inhibition of noradrenaline overflow still did not exceed that observed in the absence of physostigmine. 4. It is concluded that the vagally induced control of noradrenaline release occurs at discrete sites rather than in a diffuse pattern at multiple terminal axon sites as is the case after exogenous muscarinic agonists.

Animals↗
PubMed1982

Kinetic analysis of stimulation-evoked overflow of noradrenaline and dopamine beta-hydroxylase from the isolated rabbit heart. The effect of DOPA decarboxylase inhibition.

Rabbit isolated hearts were perfused according to a modified Langendorff procedure. Noradrenaline was measured in the venous effluents whereas dopamine beta-hydroxylase was determined in the transmyocardial fluid drained from the interstitium. Calcium-dependent release of noradrenaline and dopamine beta-hydroxylase was evoked by electrical stimulation of the heart for 6 periods of 1 min duration at 30 min intervals. Tetraethylammonium was added to enhance release. As a result of repeated stimulation, the dopamine beta-hydroxylase overflow from the heart declined monoexponentially, whereas the decline of noradrenaline was biexponential. The two phases of decline were unaltered by cocaine, an inhibitor of noradrenaline uptake. However, pretreatment of the rabbits with monofluoromethyldopa, an irreversible inhibitor of DOPA decarboxylase, transformed the biexponential decline of noradrenaline overflow into a monoexponential one with the same rate constant as that of dopamine beta-hydroxylase overflow. The sum of noradrenaline released plus that remaining in the heart was perfectly matched by the area under the curve of noradrenaline overflow values. Using the dopamine beta-hydroxylase overflow curve, the pool size of the soluble enzyme was calculated which, conversely, agreed with the enzyme contained in the 100,000 g supernatant of strongly homogenized unstimulated hearts. Before stimulation, 18% of the total dopamine beta-hydroxylase activity was in the soluble form. Stimulation depleted the hearts of noradrenaline and soluble dopamine beta-hydroxylase in a stoichiometric manner, provided that noradrenaline synthesis was blocked. The present work utilizes a novel method of measuring soluble dopamine beta-hydroxylase that is available for exocytotic release. Under the conditions of repeated stimulation and prolonged action potentials, the only factor interfering with the stoichiometry of noradrenaline and dopamine beta-hydroxylase release is the re-synthesis of noradrenaline.

Animals↗
PubMed1981

The effects of several muscarinic antagonists on pre- and postsynaptic receptors in the isolated rabbit heart.

In order to reveal possible differences between pre- and postsynaptic muscarine receptors, seven antagonists were tested for their affinities on these receptor sites in the rabbit isolated perfused heart. Methacholine was used as an agonist to inhibit the noradrenaline overflow evoked by electrical stimulation (3 Hz, 3 min) of the sympathetic nerves (presynaptic parameter) and to decrease the systolic tension development of the right atrium (postsynaptic parameter). The affinity of an antagonist was expressed as pA2. A decreasing order of potency was obtained with ipratropium, scopolamine, atropine, trihexyphenidyl, amitriptyline, and gallamine, both for pre- and postsynaptic responses. The antagonists acted competitively and their effects were reversible. Furthermore, for none of the drugs did the pA2 (pre) differ from the pA2 (post). With QNB (3-quinuclidinyl benzilate) a pA2 (post) of 11.65 was obtained. However, the affinity to presynaptic receptors could not be determined as a pA2 value due to the very prolonged exposure time required for the equilibrium with QNB and for that with methacholine in the presence of QNB. It is concluded that the antagonists employed do not reveal differences between pre- and postsynaptic muscarine receptors of the rabbit heart, in spite of their greatly varying chemical structure and their individual affinities ranging over 5 orders of magnitude. The findings confirm the view of a homogeneous muscarine receptor population characterized by functional parameters.

Animals↗
PubMed1980

The use of the De Deckere-Ten Hoor preparation for study of nicotinic and potassium-evoked dopamine beta-hydroxylase release from the rabbit heart.

1. Dopamine beta-hydroxylase (DBH) and noradrenaline were determined both in the venous effluent (perfusate) and in the transmyocardial fluid (TMF) collected from the apex of the rabbit isolated heart which was prepared according to De Deckere and Ten Hoor (1977) and perfused with Tyrode's solution at 20 ml/min. 2. Perfusion for 2 min with the nicotinic drug, p-aminophenethyl-trimethylammonium (PAPETA), both in the absence of presence of atropine evoked noradrenaline overflow into the perfusate and TMF that was maximal in the 0-2 min sample and declined from maximum with a t 1/2 of 0.6 min. DBH was released into TMF with the maximum from 2-4 min and a t 1/2 of decline of 5.6 min. 3. High K-low Na solution containing 54 mM KCl was perfused for 4 min. The maximum outputs of noradrenaline into the perfusate and TMF occurred between 2 and 4 min and that of DBH into TMF 2 min later. The t 1/2 of decline from the maxima were similar to those after PAPETA but the output ratio DBH/noradrenaline was 5 times that after PAPETA. 4. Both chemical stimuli were not observed to increase the DBH content of the perfusates. The noradrenaline concentration in the TMF was 3 times that in the perfusates. 5. It is concluded that TMF reflects concentration changes in the synaptic region more truly than the venous effluent does. TMF is particularly suitable for determination of DBH output of the heart; the DBH concentration is higher than in the perfusate and its washout faster than from the conventional Langendorff preparation.

Animals↗
PubMed1980

Peripheral muscarinic control of norepinephrine release in the cardiovascular system.

Activation of muscarinic cholinergic receptors located at the terminal adrenergic nerve fiber inhibits the process of exocytotic norepinephrine (NE) release. This neuromodulatory effect of acetylcholine and related compounds has been discovered as a pharmacological phenomenon. Subsequently, evidence for a physiological role of the presynaptic muscarinic inhibition was obtained on organs known to be innervated by the autonomic ground plexus (Hillarp, Acta. Physiol. Scand. 46, Suppl. 157: 1-68, 1959) in which terminal adrenergic and cholinergic axons run side by side. Thus, in the heart electrical vagal stimulation inhibits the release of NE evoked by stimulation of sympathetic nerves, and this is reflected by a corresponding decrease in the postsynaptic adrenergic response. On the other hand, muscarinic antagonists such as atropine enhance the NE release evoked by field stimulation of tissues innervated by the autonomic ground plexus. The presynaptic muscarine receptor of adrenergic nerve terminals probably restricts the influx of calcium ions that triggers the release of NE. However, the sequence of events between recognition of the muscarinic compound by the receptor and the process of exocytosis still remains to be clarified.

Acetylcholine↗