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S Holmgren

Publications and source records attributed to S Holmgren.

100 records · Page 6Linked to original sources

Uptake and release of catecholamines in sympathetic nerve fibres in the spleen of the cod, Gadus morhua.

The effects of drugs known from mammalian experiments to interfere with uptake and release of adrenergic transmitters in the sympathetic nerve terminals have been investigated on perfused spleen and isolated spleen strips from the cod. Cocaine and desipramine inhibit the accumulation of 3H-noradrenaline in the perfused spleen, probably by interfering with uptake mechanisms. Both drugs also shift to the left the dose-response curves for noradrenaline and adrenaline on isolated strips, cocaine being most potent. The maximal contraction force of isolated strips also increases after cocaine when noradrenaline is the agonist, but not when methacholine is used or on chronically denervated strips. This effect of cocaine is therefore not due to a general postsynaptic effect. Tyramine and amphetamine both release stored 3H-noradrenaline from the perfused spleen, and tyramine also contracted the spleen strips. In contrast to the situation in mammals, the dose-response curve for tyramine is not affected by cocaine, and tyramine (up to 10(-3) M) present in the bath does not potentiate the dose-response curve for noradrenaline on isolated strips. Different uptake mechanisms for tyramine and noradrenaline into the nerve terminal are therefore suggested for the cod sympathetic fibres. The alpha-adrenoceptor blocking agent phentolamine produces an increase in overflow of label during nerve stimulation at 5Hz in the perfused spleen preloaded with 3H-noradrenaline. An alpha-adrenoceptor-mediated control of the release of catecholamines, similar to that in mammals, appears to be present in the cod.

Amphetamine↗

Uptake and release of catecholamines in sympathetic nerve fibers in the spleen of the cod, Gadus morhua.

The effects of denervation or pretreatment with reserpine or 6-hydroxydopamine on the contractile responses of the cod spleen have been studied. The contraction produced by tyramine is abolished by pretreatment with reserpine or 6-hydroxydopamine and by denervation. The response to tyramine is restored in reserpine-treated strips after exposure to noradrenaline, but this is not the denervated or 6-hydroxydopamine-treated strips. The response to noradrenaline is potentiated by 6-hydroxydopamine treatment or denervation, while neither acute (2 days) nor chronic (8 days) reserpine treatment have any detectable effect. The effects of 6-hydroxydopamine and denervation are probably due to specific supersensitivity caused by the loss of the presynaptic uptake mechanisms on destruction of the nerve terminals, but contribution by a non-specific postsynaptic supersensitivity is not completely excluded. The effect of acetylcholine is also significantly potentiated by pretreatment with 6-hydroxydopamine or denervation, but not by reserpine, while the dose-response curve for carbachol is not affected by the specific cholinesterase inhibitor BW 284 C51, denervation or 6-hydroxydopamine. The degree of potentiation of the acetylcholine curve caused by both denervation and 6-hydroxydopamine treatment is very similar to that produced by BW 284 C51. It is concluded therefore, that the cholinesterase is associated with nerve fibres which are destroyed by denervation and 6-hydroxydopamine. Although the cod spleen receives both cholinergic and adrenergic sympathetic innervation all responses to nerve stimulation of the perfused spleen are abolished after 6-hydroxydopamine treatment. The possibility is suggested that the sympathetic fibres to the cod spleen represent a primitive type of neuron, with both catecholamines and acetylcholine present within the same terminals.

Acetylcholine↗

Autonomic nerve control of the swimbladder of the goldsinny wrasse, Ctenolabrus rupestris.

The autonomic nerve control of the swimbladder of the goldsinny wrasse has been studied by experiments with isolated strips from the muscularis mucosae, drug effects on gas secretion in vivo, fluorescent histochemistry and quantitative analysis of catecholamine content. Vagotomy, atropine and mecamylamine significantly inhibited induced gas secretion, suggesting a cholinergic vagal secretory innervation of the gas gland. The anterior part of the mucosa (secretory part) is contracted by acetylcholine and alpha-adrenoceptor agonists. These responses are competitively antagonized by atropine and phentolamine or yohimbine respectively. The posterior (resorbent) part of the mucosa is contracted by acetylcholine, but beta-adrenoceptor agonists relax the acetylcholine-precontracted preparations. These responses are competitively blocked by atropine and propranolol respectively. The pA2-values from all experiments with antagonists are well comparable with values obtained for the same drugs in other teleost or mammalian tissues. Tyramine, 5-hydroxytryptamine or phenylephrine had mixed effects on the posterior part. This effect is at least in part due to release of nervously stored catecholamines. Fluorescent histochemistry revealed a strong innervation by both smooth and varicose adrenergic fibres in all parts of the swimbladder, noradrenaline being the dominant catecholamine. Yellow fluorescent cells, which may contain 5-hydroxytryptamine, were also seen in the swimbladder mucosa. No conclusive evidence for a cholinergic innervation of the muscularis mucosae was obtained.

Acetylcholine↗

Effects of drugs and nerve stimulation on the spleen and arteries of two species of dogfish, Scyliorhinus canicula and Squalus acanthias.

The effects of drugs and nerve stimulation on the spleen of 2 species of dogfish have been examined by experiments with perfused spleens and isolated spleen and artery strips. Adrenaline, noradrenaline and phenylephrine, acting via alpha adrenoceptors, constrict the perfused spleen of both species, thereby releasing erythrocytes, and contract the isolated spleen and artery strips. Phenotolamine competitively antagonizes the excitatory effects of adrenergic agonists. The responses of the spleen to acetylcholine are very irregular, and a rapid desensitization makes evaluation of the mode of action of this drug difficult. In the artery strips acetylcholine produces a dose-dependent contraction. Fluorescent histochemistry reveals well developed adrenergic innervation of the arteries, and a few adrenergic terminals in the spleen. Stimulation of splenic nerves produces normally splenoconstriction in Squalus, which can be blocked by phentolamine but not by atropine. The nervous control of the Scyliorhinus spleen seems to be poor or lacking. It is concluded that the dogfish spleen, and maybe also the arteries, are to a large extent controlled by circulating catecholamines and (in Squalus) also by sympathetic adrenergic fibres.

Acetylcholine↗

Adrenergic innervation of coronary arteries and ventricular myocardium in the pig: fluorescence microscopic appearance in the normal state and after ischemia.

A fluorescence histochemical study was performed to describe the adrenergic innervation of the coronary arteries and the left ventricular myocardium in the pig. Large bundles of adrenergic nerve fibres were almost exclusively found running along the large coronary arteries. The arteries usually show a dense innervation of the vessel wall, evenly distributed throughout the adventitia in the larger arteries and more concentrated to the adventitia-medial border in the smaller arteries and arterioles. Most parts of the left ventricular myocardium showed a dense adrenergic innervation, however, a moderate dense and in some areas even sparse innervation was observed towards the apex of the left ventricle. Following 10 or 20 min of ischemia a small reduction in fluorescence intensity was observed in 2 out of 6 hearts. In 4 of the hearts other changes of the appearance of the adrenergic terminals were found, e.g., an unsharp, spread-out or interrupted appearance.

Adrenergic Fibers↗

Effects of some adrenergic and cholinergic drugs on isolated spleen strips from the cod, Gadus morhua.

The effects of drugs on isolated spleen strips from the cod, Gadus morhua, have been investigated. Affinities and intrinsic activities for various agonists were determined from cumulative dose-response curves. Contractions were produced by acetylcholine, methacholine or carbachol. The response to acetylcholine was considerably potentiated by the acetylcholinesterase inhibitor BW 284 C51. Methacholine-induced responses were competitively blocked by atropine (pA2 = 8.2), indicating the presence of muscarinic receptors. Nicotine did not contract the spleen strips. Adrenaline, noradrenaline or phenylephrine contracted the preparations and so did isoprenaline in high concentrations. Competitive blockade of the noradrenaline-induced contraction was obtained with yohimbine (pA2 = 6.1), phentolamine (pA2 = 6.0) and propranolol (pA2 = 3.4), and non-competitive blockade with phenoxybenzamine (pM50 = 7.0), indicating that alpha-adrenoceptors mediate the contractions produced by the adrenergic agonists. Isoprenaline caused a slight relaxation of preparations precontracted with methacholine. This effect was abolished by propranolol suggesting the presence of beta-adrenoceptors. Judged from the pA-values for the competitive antagonist, arterial and capsular/trabecular smooth muscles have slightly different alpha-adrenoceptor properties.

Adrenergic alpha-Agonists↗

Effects of ganglionic blockade on noradrenaline release and cell injury in the acutely ischemic rat myocardium.

We investigated the mechanisms responsible for ischemia-induced myocardial noradrenaline release in pentobarbitone-anaesthetized rats with left coronary artery occlusion. By means of tissue analysis of catecholamines and the Hillarp-Falck fluorescence histochemical technique for visualizing catecholamines in tissues, we studied the effect of a ganglionic blocker (chlorisondamine 0.1 mg/kg i.v.) on the ischemia-induced changes of the myocardial adrenergic nerve endings. In addition, the myocardial creatine kinase activity and potassium content were determined to estimate the extent of ischemic cell injury. In rats treated with either saline or chlorisondamine, the tissue noradrenaline content of the ischemic left ventricle was markedly reduced after 2.5 h of coronary ligation. In saline-treated rats 0.5 h of ischemia caused a slight decrease in left ventricular noradrenaline content, and this tended to be even less marked in chlorisondamine-treated animals. The changes in catecholamine fluorescence of the acutely ischemic myocardium seen after ganglionic blockade were essentially the same in both groups, but the size of the regions with reduced catecholamine fluorescence was more variable in the chlorisondamine-treated rats. Chlorisondamine caused a reduction in arterial blood pressure and heart rate and tended to reduce the degree of ischemic cell damage. We conclude that in our model the decrease in myocardial noradrenaline content after 2.5 h of ischemia is largely due to a local, nerve impulse--independent release of noradrenaline caused by ischemic changes in the tissue. The acute release of noradrenaline seen during 0.5 h of ischemia may be the combined result of local, ischemia-induced release of noradrenaline and an increased sympathetic nerve activation of the heart.

Animals↗

Neuropeptide control of the cardiovascular system in fish and reptiles.

Accumulating evidence shows the involvement of neuropeptides in cardiovascular control in mammals as well as non-mammalian species. Our own immunohistochemical studies indicate a sparse innervation only in cyclostomes, holostean fish and lungfish, a more extensive variation and distribution in elasmobranchs and teleosts, and a rich and varied innervation of the cardiovascular system in crocodiles and lizards. Vasoactive intestinal polypeptide (VIP), neuropeptie Y (NPY), gastrin releasing peptide (GRP) and tachykinins are present in most vertebrate groups. VIP is vasodilatory in the Atlantic cod (Gadus morhua) as in most mammalian species, but increases gut vascular resistance in the spiny dogfish (Squalus acanthias). NPY potentiates the effect of noradrenaline on skate (Raja rhina) coronary vessels, suggesting an interaction between adrenergic mechanisms and NPY early in evolution, but studies in the spiny dogfish and the crocodile also demonstrate different mechanisms for the action of NPY and adrenaline in some species. Bombesin/GRP increases flow to the gut in the spiny dogfish by an increase in somatic vascular resistance, while visceral resistance remains unchanged. In the caiman (Caiman crocodylus crocodylus) bombesin causes a shunting of blood from the lung to the gut. Substance P and other tachykinins in general increase flow to the gut, and on some occasions also increase somatic blood flow. Flow in the anastomosis of the crocodile (Crocodylus porosus) gut is increased by substance P. The results presented here are a review of several published and unpublished studies.

Alligators and Crocodiles↗