Role of pre- and postjunctional inhibition by prostaglandin E2 of lipolysis induced by sympathetic nerve stimulation in dog subcutaneous adipose tissue in situ.
(65/105)
1. Canine subcutaneous adipose tissue was isolated and autoperfused in situ after labelling of the noradrenaline stores by (3)H-(-)noradrenaline.2. Prostaglandin E(2) (10-200 ng/ml) increased blood flow and glucose uptake, and caused a dose-dependent inhibition of lipolysis induced by sympathetic nerve stimulation (4 Hz). The actions of exogenous prostaglandin E(2) are therefore similar to those of prostaglandin E(1) in this tissue. There were no consistent effects of prostaglandin E(2) on the vasoconstriction or on the (3)H-noradrenaline overflow induced by nerve stimulation.3. Phenoxybenzamine (1.5-2 mg i.a.) caused a 5-fold increase in (3)H-noradrenaline overflow and a 95% reduction of the vasoconstrictor response to nerve stimulation. The lipolytic response was similar to that of the control. Prostaglandin E(2) (100-200 ng/ml) administered after phenoxybenzamine caused a 90% inhibition of lipolysis, while the vasoconstrictor response was enhanced to about 50% of control. Prostaglandin E(2) inhibited (3)H-noradrenaline overflow by about 50% but it was still larger than that of the control.4. It is suggested that exogenous prostaglandin E(2) inhibits lipolysis induced by sympathetic nerve stimulation mainly by a postjunctional action in canine subcutaneous adipose tissue. (+info)
The accumulation and metabolism of (-)-noradrenaline by cells in culture.
(66/105)
1. Cultured bovine embryonic tracheal cells, EbTr (NBL-4) possess a process for the intracellular accumulation of (-)-noradrenaline with the characteristics generally ascribed to extraneuronal uptake by cardiac and smooth muscle cells in the body. It has a K(m) of 2.6 x 10(-4)M.2. The accumulation process is inhibited competitively by normetanephrine, but only at relatively high concentrations, IC50=2.1 x 10(-4)M. Inhibition also occurs with 17-beta-oestradiol, IC50=1.3 x 10(-5)M.3. The noradrenaline metabolites, 3,4-dihydroxy-mandelic acid and 3,4-dihydroxy-phenylglycol potentiate accumulation and reduce intracellular levels of normetanephrine in a similar manner to known inhibitors of catechol-O-methyl transferase.4. It is suggested that intracellular, rather than extracellular, normetanephrine may exert feedback inhibition upon noradrenaline accumulation by combining with the transport process at the inner surface of the cell membrane. (+info)
Mechanism of efflux of noradrenaline from adrenergic nerves in rabbit atria.
(67/105)
1. The mechanism of efflux of (-)-[(3)H]-noradrenaline was examined in rabbit atria, which were pretreated with reserpine and pargyline.2. Between 40 and 100 min, efflux occurred predominantly from a single intraneuronal compartment.3. Efflux was rapidy increased by (-)- and (+)-noradrenaline, tyramine and (+/-)-metaraminol, but not by (+/-)-isopropylnoradrenaline or (+/-)-normetanephrine. The increase in efflux produced by (-)-noradrenaline was inhibited by cocaine and desipramine but not by lidocaine.4. Spontaneous effluxes, and those accelerated by (-)-noradrenaline, were temperature-sensitive.5. Efflux was increased by ouabain, omission of K(+), metabolic inhibition and lowering of the external Na(+) concentration. These effects were significantly reduced by cocaine and desipramine but not by lidocaine.6. These findings provide evidence that the efflux of [(3)H]-noradrenaline from adrenergic nerves occurs by a cocaine-sensitive, carrier-mediated process. The characteristics of the efflux process are compatible with, but not conclusive proof for, the Na(+)-gradient hypothesis. (+info)
An examination of the negative feedback function of presynaptic adrenoceptors in a vascular tissue.
(68/105)
1 The hypothesis was examined that presynaptic alpha-adrenoceptors exert a negative feedback function regulating noradrenergic transmission.2 Renal artery strips from cattle, pre-incubated with [(3)H]-noradrenaline, were stimulated with 300 pulses at 5 different frequencies, spanning the physiological range, and the efflux of tritium assessed both in the absence and presence of functional presynaptic receptors.3 Considerable variation in the synaptic level of free and active noradrenaline with increasing frequency was apparent from the rates of development and the magnitudes of the mechanical responses but the overflow of tritium was constant at 1, 2, 10 and 15 Hz and slightly elevated at 5 Hz, providing no evidence for presynaptic modulation of release.4 Phenoxybenzamine (3.3 x 10(-5) M) enhanced the overflow of tritium most at the lowest frequency tested and to a similar extent at the other test frequencies, except 10 Hz where its effect was slightly reduced.5 The conditions of the present experiments appeared optimal for the operation of the negative feedback system and the failure to observe an increased effectiveness of the antagonist with increasing frequency indicates that the physiological relevance of such a system is highly questionable and suggests that it may not function at all. (+info)
Hypothalamic endogenous noradrenaline and thermoregulation in the cat and rabbit.
(69/105)
1. The imino-dibenzyl drugs, imipramine and desipramine, which inhibit the uptake by neurones of noradrenaline, were injected into the lateral cerebral ventricles of cats and rabbits: changes in body temperature resulted which were different for the two species, but nevertheless closely resembled those following intraventricular injection of relatively large quantities of exogenous noradrenaline.2. The endogenous noradrenaline content of the hypothalamus in both species was reduced by repeated injections into the lateral ventricle of the methyl ester of DL-alpha-methyl-p-tyrosine: in animals so treated the hypothalamic content of 5-hydroxytryptamine was not significantly changed.3. Noradrenaline-depleted animals showed significantly reduced responses to intraventricular imipramine and desipramine. The diminished responses were primarily due to reduction in endogenous noradrenaline.4. These observations indicate that endogenous noradrenaline, present in the hypothalamus, can influence body temperature in cats and rabbits. (+info)
Relaxing effects of catecholamines on mammalian heart.
(70/105)
1. The effect of catecholamines on the time course and amplitude of contraction and on KCl-induced contractures has been studied in mammalian hearts.2. Marked and reproducible contractures could be obtained in mammalian ventricular trabeculae and papillary muscles after beta-adrenergic block with propanolol or if the hearts were depleted of their catecholamine stores by reserpine or by chemical denervation with 6-hydroxydopamine.3. In neonatal hearts with lower endogenous catecholamine stores and poorly developed sarcoplasmic reticulum KCl contractures are easily produced.4. Catecholamines potentiate twitch tension and relax the contracture tension under all of the above circumstances.5. The relaxant effect of catecholamines is present during the time course of a twitch. This increased relaxation rate as well as the shortening of the time-to-peak of tension is independent of the variation in the duration of the action potential.6. The shortened relaxation time is present when the action potential is shortened with anodal repolarization or prolonged with cathodal depolarization (voltage-clamp).7. The relaxant effect of catecholamines on the twitch is temperature and rate dependent. The effect is observed in the presence of high or low concentrations of calcium.8. The presence of catecholamines is necessary for full relaxation of mammalian heart muscle under high performance conditions or states of calcium overload.9. It is proposed that catecholamines exert their relaxant effect independent of their positive inotropic effect by stimulating the sequestering system (sarcoplasmic reticulum, mitochondria or sarcolemma) for calcium. (+info)
Actions of dexamphetamine and amphetamine-like amines in chickens with brain transections.
(71/105)
1. A method for preparing the encephale isole preparation in young fowls is described. Certain important differences were found between electrocortical activity of chicken and mammalian encephale isole preparations. Electrocortical effects of excitant sympathomimetic amines and their antagonism were readily quantified because of stable electrocortical activity of the chick encephale isole preparation.2. Amphetamine-like excitant amines ((+)- and (-)-amphetamine, alpha-methyltryptamine, tryptamine, beta-phenethylamine, cyclopentamine, beta-tetrahydronaphthylamine and tuaminoheptane) evoked electrocortical desynchronization in chick encephale isole preparations, confirming the central origin of these effects. Behavioural changes were also observed.3. The electrocortical response to these amines was antagonized by methysergide, a selective tryptamine antagonist and by a catecholamine, alpha-methylnoradrenaline. Behavioural changes were also antagonized.4. Electrocortical desynchronization to dexamphetamine was prevented by an anterior transection of the brain which separated the telencephalon from the diencephalon. More posterior transections reduced the duration of the electrocortical response to dexamphetamine; intensity of response was either increased or decreased. (+info)
Noradrenaline uptake by non-innervated smooth muscle.
(72/105)
1. Uptake of noradrenaline (NA) into the non-innervated smooth muscle cells of the human umbilical artery and the chick amnion has been studied with the fluorescence histochemical technique for localizing monoamines. Comparison has been made with uptake into sympathetically innervated smooth muscle of the rabbit ear artery.2. Accumulation of NA within non-innervated smooth muscle cells is observed histochemically after exposure to much lower concentrations of NA (10(-7) g/ml) than in sympathetically innervated smooth muscle cells, where accumulation occurs with NA (10(-5) g/ml).3. In contrast to innervated smooth muscle, uptake of NA (10(-4) g/ml) by non-innervated smooth muscle is characterized by lack of inhibition by phenoxybenzamine, normetanephrine and cold, although some inhibition is apparent at lower NA concentrations. Retention of NA during prolonged washing in NA-free Krebs demonstrates that it is strongly bound within the non-innervated smooth muscle cells, particularly in the nucleus.4. After inhibition of catechol-O-methyl transferase, the accumulation of NA in innervated smooth muscle closely resembles that in non-innervated smooth muscle. (+info)