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K B Helle

Publications and source records attributed to K B Helle.

At least 55 records · Page 3Linked to original sources
PubMed1987

Comparison of VIP and beta 2-adrenoceptor-induced relaxations in the circular and longitudinal smooth muscle layers of the rat portal vein.

The relative importance of VIP in reduction of vascular tone was studied in circular and longitudinal preparations of the VIP-innervated rat portal vein. Exogenous VIP inhibited the methoxamine-evoked contractures in the atropine-blocked preparations with a lower potency in the inner, circular (pD2 = 6.4 +/- 0.5, n = 6) than in the outer, longitudinal layer (pD2 = 7.7 +/- 0.1, n = 6). VIP was also a less efficient relaxant (intrinsic activity (alpha) = 0.60 +/- 0.16, n = 6) of the inner than of the outer layer (alpha = 1.00). The selective (salbutamol) and the non-selective (isoproterenol) beta 2-agonists completely relaxed the methoxamine contractures in both layers and the potency (isoproterenol) was higher in the inner (pD2 = 6.39 +/- 0.32, n = 6) than in the outer layer (pD2 = 5.67 +/- 0.34, n = 6). Plasma from the portal-mesenteric vein of anaesthetized, fasting rats contained 0.036 nM VIP (median, n = 17), that is, several orders of magnitude lower than the range of VIP concentrations relaxing the methoxamine contracted vein preparations via VIP receptors of the apamin-blockable category. The results support the hypothesis that alpha 1-adrenoceptor-induced contractions in the circular layer are predominately relaxed via beta 2-adrenoceptors while relaxation of the outer layer may occur via VIP receptors, probably activated by local release of the neuropeptide.

Albuterol↗
PubMed1987

Functional alpha-adrenoceptors in human atrial preparations in the presence of beta-receptor blockade.

Inotropic effects via cardiac alpha-adrenoceptors were studied in electrically driven auricular strips (1 Hz, 37 degrees C) from patients treated with beta-blockers for months prior to open heart surgery. Marked alpha-mediated positive inotropic effects were demonstrated with adrenaline (A), noradrenaline (NA) and phenylephrine (PHE) in the presence of beta-blocker and with blockers of the muscarinic receptor and of the neuronal and extraneuronal uptake mechanisms for the catecholamines. In the presence of approximately 10(-6) M propranolol the maximal effects as well as the potencies (pD2-values) for A and NA were not significantly different while higher than for PHE. The alpha 1-blocker, prazosin (10(-6) M), markedly reduced the pD2-values but not the intrinsic activities (alpha-values) for A, NA and PHE in the beta-blocked preparations. Methoxamine, however, induced negative inotropic responses at normal and low frequencies (1, 0.5 and 0.1 Hz) of stimulation, suggestive of non-specific, cardiodepressant effects. Other agonists with alpha-effects in other types of tissue (oxymethazoline, xylomethazoline and clonidine) were without effects on the force and velocity of contraction in the auricular strips under the present experimental conditions. The results show alpha 1-type of adrenoceptor-induced inotropic effects for A, NA and PHE during beta-blockade in human auricular strips, indicating that cardiac alpha 1-receptors may have clinical importance by increasing the inotropy of the human myocardium treated with beta-blocking agents.

Adrenergic alpha-Agonists↗
PubMed1986

Activation of cardiac beta 2 adrenoceptors in the human heart.

Comparative pharmacologic studies have indicated that the cardiac beta 2 adrenoceptors of vertebrate species are "adrenaline" receptors; i.e., the distribution of beta 2 receptors in the heart seems to be related to the amounts of adrenaline in the sympathetic nerves and in the circulation, and the beta 2 receptors seem to be stimulated mainly by adrenaline. In the human right atrium the order of potency for the agonists and the blocking agents indicate a relatively high proportion of active beta 2 receptors. These findings are in agreement with radioligand binding studies demonstrating up to 50% beta 2 receptors in myocardial membrane preparations. The pharmacologic studies thus add support to the assumption that these beta 2 receptors are functionally active and not merely experimental oddities. It is hypothesized that in normal situations the beta 2-receptor effects are additive to the beta 1 effects. However, during acute stress situations the large amounts of released adrenaline are assumed to increase markedly both inotropy and chronotropy in the heart via beta 2 receptors. It is postulated that only unselective beta blockers can abolish all beta-receptor effects in the heart during stress reactions with profound catecholamine stimulation.

Adrenergic beta-Agonists↗
PubMed1985

Postnatal ontogenesis of the dopaminergic innervation in the rat anterior cingulate cortex (area 24). Immunocytochemical and catecholamine fluorescence histochemical analysis.

The postnatal development of the dopaminergic input to the rat anterior cingulate cortex (area 24) was followed using anti-tyrosine hydroxylase immunocytochemistry and catecholamine fluorescence histochemistry in control and noradrenaline-depleted rats. Noradrenaline depletion in the cerebral cortex was obtained by peripheral injections of 6-hydroxydopamine (6-OHDA) at birth or N-2-chloroethyl-N-ethyl-2-bromobenzylamine (DSP4) at various postnatal ages and controlled by the absence of dopamine-beta-hydroxylase-labelled axons. The superficial and deep components of the anterior cingulate dopaminergic field developed at a different rate in control as well as lesioned rats. The deep supragenual dopaminergic field was already present at birth like the dopaminergic innervation of the prefrontal cortex area 32. In the superficial field, the molecular layer was reached first from postnatal day 3 (P3) on by positive axons running through the anterior hippocampal continuation and from P5-P6 on by another dopaminergic contingent coming through the deep dopaminergic field and giving off collaterals for layer III. The adult distribution pattern and striking varicose aspect were not reached until P21-P30 and a further increased density was observed until P60. The superficial cingulate dopaminergic field extended into the pregenual part of area 24b. The innervation of the superficial and deep layers of the rat anterior cingulate cortex by two distinct dopaminergic subpopulations, one of them closely related to that of prefrontal cortex area 32, could be compared with other laminar differences. The important functional implications of these data are further discussed.

Adrenergic Fibers↗
PubMed1985

Calcium paradox from cyclostome to man: a comparative study.

In seven poikilotherm species, i.e. cyclostome, Myxine glutinosa; teleosts, Gadus morrhua; Platichtys flesus; amphibia, R. pipiens; R. temporaria; Xenopus laevis; reptiles, Vipera berus. Ca paradox could not be obtained in ventricular strips at 8-12 degrees C. In similar preparations from human atria at 30 degrees C and 37 degrees, Ca paradox was obtained similarly as in other homoiotherms. In homoiotherms, lowered temperature (below 30 degrees C) has a protective effect. Viper myocardium did not display Ca paradox at 12, 22 or 32 degrees C, whereas human myocardium displayed Ca paradox even at 30 C. It is postulated that the absence of Ca paradox in poikilotherms is not due to the low temperature. In hagfish (Myxine glutinosa) the absence of Ca paradox seems to be due to the specific conditions concerning Ca exchange in the myocardial cell (large glycocalyx).

Animals↗
PubMed1985

New dopaminergic terminal fields in the motor, visual (area 18b) and retrosplenial cortex in the young and adult rat. Immunocytochemical and catecholamine histochemical analyses.

New dopaminergic terminal fields have been visualized in the rat cerebral neocortex, using two morphological methods based on distinct properties of the dopaminergic system: presence of the first synthetic enzyme, tyrosine hydroxylase, and high-affinity uptake of amines. Tyrosine hydroxylase was used as an immunocytochemical marker after destruction of the cortical noradrenergic system, induced either neonatally by 6-hydroxydopamine or later on by DSP4, and controlled by the absence of dopamine beta-hydroxylase immunoreactivity. The uptake and storage of exogenous amines in tissue sections, in the presence of selective high-affinity transport inhibitors, enabled the specific visualization of the dopaminergic system with fluorescence histochemistry. A dopaminergic innervation of low density was observed along a dorsal sagittal strip which extended from the genu of corpus callosum until about 2 mm behind the splenium and encompassed several distinct cytoarchitectonic areas in the sensorimotor and visual cortex (medial and lateral agranular field, area 18b), as well as in discrete zones of the retrosplenial granular 29c,b, and agranular 29d areas. The distribution of these dopaminergic fields suggested a columnar organization. Several characteristics of the dopaminergic innervation were similar to that of the superficial anterior cingulate cortex (area 24): the laminar distribution to the superficial I-III layers, the secondarily developed varicose aspect in catecholamine fluorescence histochemistry and the delayed postnatal ingrowth in contrast with the early prenatal dopaminergic input to the prefrontal cortex. These similarities suggested that the subpopulation of dopaminergic neurons which provides projections to the anterior cingulate cortex could also contribute to the motor and visual cortex and thus play a role in sensorimotor integration. The predictive value of these results in the ascent of the phylogenetic scale are further considered.

Aging↗
PubMed1985

Morphological evidence for a dopaminergic terminal field in the hippocampal formation of young and adult rat.

We have visualized the dopaminergic innervation of the hippocampal formation of the rat using two morphological methods: (1) tyrosine hydroxylase immunocytochemistry on noradrenaline-depleted animals and (2) fluorescence histochemistry after the uptake and storage of dopamine on hippocampal slices in vitro. The noradrenergic hippocampal terminal fields were destroyed by neonatal neurotoxin pretreatment and the validity of the lesion checked by the absence of dopamine beta-hydroxylase immunoreactivity. As observed on early postnatal ages, dopaminergic axons reached the hippocampal formation through the fimbria and the alveus, but also through the supracallosal bundle and the ventral amygdaloid area-entorhinal cortex. The temporal (ventral and caudal) part of the hippocampal formation received the bulk of the dopaminergic innervation whereas no fibers were observed in the septal pole. Very few positive axons were visualized in the hilus of the gyrus dentatus and CA3 field, only near the temporal pole. CA1 field (stratum oriens) was innervated throughout its ventral part. The most innervated area was the ventral part--especially the deep layers--of the subiculum, in particular the prosubiculum. The dorsal part of the subiculum displayed some positive axons, although to a lesser extent. The pre- and parasubiculum contained a few positive axons. In addition, some immunoreactive axons were observed in the anterior hippocampal continuation and the indusium griseum. The ventral junction prosubiculum-CA1 field appears to be the main target area for the hippocampal dopaminergic innervation. It is interesting that the same areas are characterized by their projections to the nucleus accumbens which receives dopaminergic afferents. Thus, the hippocampostriatal projections, that represent a link between the limbic and central motor mechanisms, could be under dopaminergic influence.

Age Factors↗
PubMed1985

Osmotic properties of the chromogranins and relation to osmotic pressure in catecholamine storage granules.

The soluble proteins (chromogranins) of bovine chromaffin granules have been studied by micro-osmometry with semi-permeable membranes (UM2, PM10 and PM30 with cut-offs greater than 1, greater than 10 and greater than 30 kD, respectively) at 1 = 0.15 and pH 5-8 for protein concentrations up to 20 mg X ml-1. After lysis of chromaffin granules in phosphate buffer pH 6, the released chromogranins behaved as aggregating solutes, consistent with an inconspicuous osmotic pressure contribution from the chromogranins at the protein concentration of the intact granules. Thus, in the presence of phosphate about 90% of the molecules behaved as colloids with Mr = 30,300 at c = o. After lysis in phosphate-free buffers the chromogranins behaved as highly non-ideal solutes in a manner which was incompatible with isotonicity at the protein concentration of the intact granules. About two-thirds of the molecules in the lysates in Na-succinate pH 5-6 and K-acetate pH 6 exhibited Mr = 66,000 and 79,000, respectively. In dilute solutions (less than 12 mg protein X ml-1) and ATP/protein ratios corresponding to those in the intact granules, the UM2 pressures were markedly increased, indicating release of polypeptides with Mr 2000-3000 from aggregates. CaCl2 was without specific effect on the colloid osmotic pressures but reduced the ATP-dependent increase in pressure, suggesting release of molecules twice the size of those released by ATP alone. A model is presented for the contribution of the chromogranins to osmotic pressure regulation in the bovine adrenomedullary catecholamine-storing granules.

Adenosine Triphosphate↗
PubMed1985

Functional beta 1- and beta 2-adrenoceptors in the human myocardium.

Functional beta-adrenoceptor populations in the human heart were studied in vitro in electrically-paced strips of the right auricular and ventricular myocardium. The relative potency of selected agonists in producing inotropic responses (Tmax, T'max) in the presence of blockers for neuronal and extraneuronal uptakes was found to be as follows: isoprenaline greater than noradrenaline = adrenaline = salbutamol greater than dobutamine. Prenalterol had a negative inotropic effect in these preparations. The selective beta 1-(practolol) and beta 2-(H 35/25) blockers reduced inotropic responses to adrenaline (Tmax, T'max) and noradrenaline (T'max) in the auricular strips. These results indicate the participation of beta 2-adrenoceptors in inotropic responses in the human auricular and ventricular myocardium. For comparison, inotropic responses of electrically-paced rat myocardium to beta-adrenergic agonists in the presence of blockers for neuronal and extraneuronal uptakes were likewise studied. The relative potencies for Tmax were: noradrenaline = adrenaline greater than prenalterol greater than dobutamine = salbutamol. Given the high relative potency of salbutamol in the human myocardial strips (analogous to that previous shown in the beta 2-dominated atria of the frog and trout) and the low relative potency of salbutamol in the rat tissue, these findings indicate a greater population of functionally active beta 2-adrenoceptors in the human than in the rat myocardium.

Adrenergic beta-Agonists↗
PubMed1985

Effects of calcium and limited proteolysis on membrane-bound and releasable dopamine beta-hydroxylase in adrenomedullary catecholamine granules.

Bovine chromaffin granules were shown to contain two potent proteolytic systems resulting in limited proteolysis of granule proteins at pH 6.0 in the cold in the presence of inhibitors of serine and thiol proteases. Calcium, whether added during lysis or remaining bound to the lysate protein during dialysis in non-chelating solutions, enhanced recoveries of total immunoreactive dopamine beta-hydroxylase (14% of total protein) and soluble enzyme (9% of lysate protein) due to degradation of of chromogranins. A pepstatin A-blockable, catepsin D-like proteolytic system converting membrane-bound enzyme to its soluble counterpart at pH 6.0 was detected in the granule membrane fraction.

Adrenal Medulla↗
PubMed1984

Membrane dopamine beta-hydroxylase: a precursor for the soluble enzyme in the bovine adrenal medulla.

Searching for endogenous proteolytic activities converting the membrane form of dopamine beta-hydroxylase (dopamine beta-monooxygenase, DBH) into the soluble and releasable form, DBH was monitored enzymatically and immunologically in aqueous and detergent-solubilized extracts of the adrenomedullary fractions. Degradation of the soluble DBH and acidic chromogranins by activation of endogenous proteases occurred during lysis in H2O. Shifts in the hydrophobicity of the membrane DBH were also apparent. Loss in enzyme protein or activity was, on the other hand, not observed for buffer-dialysed CG (pH 5-6). Limited proteolysis within the membrane phase was, however, indicated by the shift towards dominance of the intermediate hydrophobic DBH in the buffer-dialysed CG. By two-dimensional, crossed immunoelectrophoresis with cationic detergent the microsomal DBH was immunologically identical to the granule-bound enzyme but differed from the latter in molecular heterogeneity and in susceptibility to proteolytic solubilization by endogenous protease activities. DBH in the membranes of the chromaffin granules was proteolytically solubilized at pH 6-8 and the soluble DBH further degraded at pH 5. The results indicate that a post-translational conversion of the amphiphilic DBH into the soluble form, initiated at the level of the microsomes, may continue within the light and the heavy granule fractions which contain several DBH-converting and degrading proteolytic activities with acid optima.

Adrenal Medulla↗
PubMed1984

Absence of calcium paradox in the cardiac ventricle of the Atlantic hagfish (Myxine glutinosa).

Spontaneously beating strips of the cardiac ventricle of the cyclostome Myxine glutinosa were characterized with respect to dependence on extracellular calcium for the cardiac contractility at 8 degrees C. The force developing (Tmax) was reduced by 20-50% when exposed to calcium-free medium (+/- 10(-3)M EDTA) for 15-60 min. Return to normal Myxine Ringer (4.5 mM Ca2+) resulted in 120-130% recovery to Tmax without change in resting tension. These experiments show that the heart of this primitive vertebrate, analogous to that of other poikilotherms, does not display the "Ca-paradox" phenomenon. Being relatively insensitive to changes in extracellular Ca2+ the Myxine myocardium differs from that in most poikilotherms in other respects, e.g. in the mechanisms regulating beat to beat changes in intracellular Ca2+.

Animals↗
PubMed1984

In search of mediators of skin vasodilation induced by transcutaneous nerve stimulation: IV. In vitro bioassay of the vasoinhibitory activity of sera from patients suffering from peripheral ischaemia.

The widespread cutaneous vasodilation which can be induced by low-frequency transcutaneous nerve stimulation (TNS) in humans is, at least in part, due to sympatho-inhibition. Studies on the additional involvement of an active local vasodilator have demonstrated a moderate increase in plasma vasoactive intestinal polypeptide (VIP) but excluded a series of known dilators. In the present study sera from four patients with peripheral ischaemia (three with Raynaud's disease, and one with diabetic polyneuropathy) were assayed for vasoactivity on isolated vascular smooth muscle (rat portal vein) with reactivity towards a wide series of classical neurotransmitters and neuropeptides. In the presence of cholinergic and beta-adrenergic blockade sera collected after TNS-induced vasodilation revealed an inhibitory activity which could not be accounted for by changes in osmolarity, pH or K+. The inhibitory response to the plasma samples developed more rapidly than the response to synthetic VIP. The inhibitory activity of the plasma samples excluded a series of other peptides such as substance P, neurotensin, pancreatic polypeptide, bradykinin and angiotensin II, which all enhanced the contractile activity in the rat portal vein. There was a proportional increase in skin temperature and occurrence of inhibitory activity in cubital plasma samples in response to TNS. The results suggest that a peripheral vasodilator activity besides VIP may be implicated in the sustained dilation induced by TNS in these patients.

Adult↗
PubMed1984

VIP inhibition of vascular smooth muscle: complementary to beta 2-adrenoceptor mediated relaxation in the isolated rat portal vein.

Exogenous VIP caused a concentration dependent inhibition of the spontaneous mechanical activity in the isolated rat mesenteric-portal vein preparation via a mechanism which was completely independent of the propranolol-blocked beta-adrenoceptor, of high K+ in the medium and of exogenous bovine pancreatic polypeptide, neurotensin and opioids. The potency of VIP (pD2 = 7.52 +/- 0.18, n = 6) was about 30 times higher than that of isoprenaline in the atropine and phentolamine-blocked preparation. The isoprenaline inhibition was mediated via a beta 2-type of adrenoceptor with low apparent affinity for noradrenaline (intrinsic activity (alpha) = 0.27 +/- 0.01, n = 8). Opposite effects of exogenous VIP and noradrenaline were on the other hand observed in the atropinized and beta-blocked preparation. These results suggest that in the rat portal vein neuronal VIP and circulating adrenaline may be complementary in their antagonism of the alpha-adrenoceptor mediated increase in contractility.

Adrenergic beta-Agonists↗
PubMed1983

Structural organization of the normal and anoxic heart of Scyllium stellare.

The general and ultrastructural organization of the heart of the elasmobranch, Scyllium stellare, was studied in normal and in anoxic animals. The rich coronary supply was revealed three-dimensionally by the use of corrosion casts, showing a thebesian system of coronary arterioles and capillaries in the thin, outer compact layer as well as in the predominant, inner spongy layer of trabeculae. Only the sinus venosus received a neuronal input of large bundles of granule-containing axons terminating at fenestrated regions of the endocardium and suggesting a neurohormonal function. A simple, tubular sarcoplasmic reticulum with flattened junctional cisternae was present in myocardial cells of 1-5 microns diameter, which contained one or two bundles of myofibrils. The latter were closely apposed to the inner aspect of the plasmalemma. Mitochondria were located centrally in the cells, which were joined by unfolded desmosomes involving Z-band material. Long periods of anoxia were tolerated without loss of heart function, but at the expense of cytoplasmic glycogen. Lipid granules were abundant in all layers and chambers, notably in animals prepared in the summer. The lipid granules displayed a marked increased in electron density when the heart was incubated in a buffered oxalate solution prior to fixation. A glycogen-sparing effect of the lipids during anoxia was observed.

Animals↗
PubMed1982

Neurotensin receptors in the rat bronchi.

The isolated, circular preparations of the left and right bronchi of the rat were examined for mechanical responses to neurotensin (NT) and other vasoactive peptides. NT caused concentration-dependent increases in the isometric tension of the unstimulated preparations, with an apparent affinity higher than for the cholinergic agonists but with considerably lower intrinsic activity. Pronounced tachyphylaxis to NT was observed. NT potentiated the atropine-sensitive increase in tension resulting from electrical field stimulation. Neither atropine nor methysergide abolished the response to NT in the unstimulated preparations. Bradykinin and to a lesser extent angiotensin II contracted the unstimulated preparations and both systemic peptides enhanced the cholinergic output in response to field stimulation. Substance P and VIP on the other hand were without effects in the stimulated and unstimulated bronchi. The results are consistent with the presence of receptors for NT on the presynaptic cholinergic terminals as well as on the post-synaptic smooth muscles of the rat bronchi.

Angiotensin II↗