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Biomedical subjects

S Holmgren

Publications and source records attributed to S Holmgren.

At least 91 records · Page 5Linked to original sources

Neuropeptide functions in the fish gut.

Several neuropeptides, more or less related to their mammalian counterparts, are present in the enteric nervous system in fish, and may function as neurotransmitters, cotransmitters or neuromodulators in this system. Excitatory effects on fish gut smooth muscle are found with bombesin, substance P and neurotensin. VIP and bombesin are inhibitory in some preparations and metenkephalin and somatostatin give varying responses. Of the more closely studied neuropeptides, a bombesin-like peptide may be involved in a cofunction with acetylcholine in the excitation of gut motility. One or more tachykinins may be involved in different mechanisms controlling the gut motility, directly or indirectly via, e.g., serotonergic neurons. Bombesin, a tachykinin and VIP may control gastric secretion, and VIP may have vasodilatory functions as well as inhibitory functions on gut motility at least in some species.

Animals↗

Substance P acts by releasing 5-hydroxytryptamine from enteric neurons in the stomach of the rainbow trout, Salmo gairdneri.

The effect and mode of action of substance P was studied in a perfused stomach preparation and on isolated strip preparations of the stomach wall from the rainbow trout, Salmo gairdneri. Substance P was excitatory on the stomach muscle wall in a dose-dependent manner. Two other tachykinins, physalaemin and eledoisin, excited the preparations in a similar manner and in the same dose range. The effect of substance P was not antagonized by the substance P analogues [D-Pro2, D-Phe7, D-Trp9]substance P and [D-Pro2, D-Trp7,9]substance P (both 10(-5) M). Tetrodotoxin reduced or abolished the effect of substance P, while no reduction of the response was obtained after atropine, chlorisondamine or phentolamine (all 10(-6) M). 5-Hydroxytryptamine excited the stomach and this effect was not antagonized by tetrodotoxin, suggesting that the action of 5-hydroxytryptamine was direct on the smooth muscle. The 5-hydroxytryptamine antagonist methysergide, in a concentration which selectively blocked the response to 5-hydroxytryptamine, also blocked the response to substance P (10(-9)-10(-8) M). The outflow of 5-[3H]hydroxytryptamine from a preloaded perfused stomach was clearly increased by substance P, and this release was blocked by tetrodotoxin. Immunohistochemistry revealed the presence of nerve fibres and ganglion cells showing 5-hydroxytryptamine-like immunoreactivity in the myenteric plexus and smooth muscle layers of the stomach wall. The immunoreactive cells and nerve fibres were particularly abundant in the pyloric part of the stomach. It is concluded that the main effect of substance P on the stomach wall of the rainbow trout is indirect, via activation of a non-adrenergic, non-cholinergic neuron. The results are compatible with the view that this neuron exerts its action by release of 5-hydroxytryptamine. Supramaximal concentrations (greater than or equal to 10(-7) M) of substance P may in addition have a direct effect on the gastric smooth muscle.

Animals↗

D- and L-isoprenaline have different effects on adrenoceptors in the systemic vasculature of the cod, Gadus morhua.

The effects of D- and L-isoprenaline on systemic vascular adrenoceptors of the cod was studied using blood pressure recording from conscious cod in vivo and isolated coeliac artery strip preparations in vitro. Experiments with isolated artery preparations demonstrated that the D-, but not the L-isomer of isoprenaline acts as an alpha-adrenoceptor antagonist. A dose-dependent reduction of ventral and dorsal aortic blood pressures together with a dose-dependent increase in the heart rate could be produced by injection of L-isoprenaline. D-Isoprenaline, on the other hand, had no effect on the blood pressures or heart rate except in the highest dose injected. The results show an alpha-adrenoceptor blocking capacity of D-isoprenaline in the cod. The effect of L-isoprenaline on the blood pressure supports the idea that the hypotensive effect of DL-isoprenaline seen in previous studies of the cod may be attributed to an effect of the L-isomer on beta-adrenoceptors mediating vasodilation of the cod systemic vasculature.

Animals↗

Neurotransmitters in the intestine of the Atlantic cod, Gadus morhua.

The effects of the putative neurotransmitters acetylcholine, adrenaline, adenosine, ATP, bombesin, 5-hydroxytryptamine, met-enkephalin, neurotensin, somatostatin, substance P and VIP have been investigated in the perfused intestine of the cod, Gadus morhua. The presence and distribution of the different types of nerves was investigated with immunohistochemistry and Falck-Hillarp fluorescence histochemistry. A spontaneous rhythmic activity of the perfused preparations usually occurred within a few minutes from the start of the experiment. This activity was diminished or abolished by addition of atropine, methysergide or tetrodotoxin to the perfusion fluid. Acetylcholine, 5-hydroxytryptamine or substance P caused a contraction of the intestinal wall. The response to acetylcholine was blocked by atropine but not by tetrodotoxin, while the response to 5-hydroxytryptamine was blocked by methysergide and usually also by tetrodotoxin. This indicates that the effect of acetylcholine is direct on the muscle cells, while the effect of 5-hydroxytryptamine may be at least partly via a second neuron. All adrenergic agonists (adrenaline, isoprenaline and phenylephrine) had a dominating inhibitory effect on the intestine. Experiments with antagonists showed that the inhibition is due to stimulation of both alpha-adrenoceptors and beta-adrenoceptors. ATP, adenosine and somatostatin also caused a relaxation of the intestinal wall, often followed by a contraction. Met-enkephalin produced variable responses, either a relaxation, a contraction or both. Bombesin caused a weak inhibition, if anything. Neurotensin and VIP did not visibly affect the intestinal motility. 5-HT-, substance P- and VIP-like immunoreactivity and catecholamine fluorescence were observed in the myenteric plexus, submucosa and muscle layers in all parts of the intestine.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗

Bombesin-, gastrin/CCK-, 5-hydroxytryptamine-, neurotensin-, somatostatin-, and VIP-like immunoreactivity and catecholamine fluorescence in the gut of the elasmobranch, Squalus acanthias.

The presence of peptides and 5-hydroxytryptamine (5-HT) in neurons and endocrine cells in the gastrointestinal tract of the spiny dogfish, Squalus acanthias, was investigated by means of immunohistochemistry, and the distribution of catecholamines by use of the Falck-Hillarp fluorescence-histochemical technique. Bombesin-like immunoreactivity was present in numerous nerves in all layers and all parts of the gut, and also in endocrine cells in the mucosa throughout the stomach, rectum and intestine. VIP-like immunoreactivity occurred in an abundance of nerve fibres and in nerve cell bodies in all parts of the gut except the oesophagus, while 5-HT-like immunoreactivity was found sparsely in nerve fibres and more frequently in endocrine cells throughout the gut. Gastrin/CCK-like immunoreactivity was present in numerous nerve fibres in the rectum, but only in scattered fibres in the other parts of the gut. Endocrine cells showing gastrin/CCK-like immunoreactivity were present in the intestine only. Somatostatin-like immunoreactivity occurred in both nerve fibres and endocrine cells of the stomach and intestine, but only in nerves in the rectum. Neurotensin-like immunoreactivity was confined to endocrine cells of the intestine. Falck-Hillarp fluorescence histochemistry revealed 5-HT in endocrine cells and catecholamines in nerve fibres (and possibly also in endocrine cells) throughout the gut. Bombesin-, VIP-, gastrin/CCK- and somatostatin-like immunoreactivities and catecholamine fluorescence were present in nerve fibres of the rectal gland and, with the exception of gastrin/CCK-like immunoreactivity, also in nerve bundles in the walls of the coeliac and mesenteric arteries. The findings of the present study form an anatomical basis for the assumption that several of the neuropeptides and amines could function as neurotransmitters or neuromodulators in the gut of Squalus.

Animals↗

Splanchnic nervous control of the stomach of the spiny dogfish, Squalus acanthias.

The splanchnic innervation of the stomach of Squalus acanthias has been studied using an isolated perfused stomach preparation and isolated strip preparations from the smooth muscle of the stomach wall. The stomach contracted in response to splanchnic nerve stimulation, and this response was mimicked by all three putative transmitter substances tested: adrenaline, acetylcholine and 5-hydroxytryptamine. The response to nerve stimulation was not affected by atropine (10(-6) M) or methysergide (10(-6) M), but was abolished by phentolamine (10(-6) M). This concentration of phentolamine had little or no effect on the responses of the stomach to exogenous acetylcholine or 5-hydroxytryptamine, but significantly blocked the response to exogenous adrenaline. The results are interpreted in favour of an adrenergic excitatory splanchnic innervation of the dogfish stomach. A "rebound" contraction of the stomach normally occurred upon cessation of the splanchnic nerve stimulation. This response disappeared together with the primary contraction after administration of phentolamine, suggesting the involvement of an adrenergic mechanism in the occurrence of the "rebound" contraction in this preparation. The present experiments did not provide any conclusive evidence for a splanchnic nervous control of the gastric vasculature.

Acetylcholine↗

The effects of putative non-adrenergic, non-cholinergic autonomic transmitters on isolated strips from the stomach of the rainbow trout. Salmo gairdneri.

1. The effects of some putative non-adrenergic, non-cholinergic transmitters have been studied on longitudinal and circular smooth muscle from the stomach of the rainbow trout, Salmo gairdneri. 2. ATP, adenosine and vasoactive intestinal polypeptide (VIP) on certain occasions inhibited the activity of the stomach smooth muscle; ATP and adenosine only circular muscle. VIP both longitudinal and circular muscle. 3. Neurotensin produced a contraction, which in strips from the cardiac stomach in most cases occurred after the exposure to the peptide; this might be a rebound contraction after an inhibition which could not be recorded with the experimental set-up. 4. Bombesin, 5-hydroxytryptamine and substance P produced dose-dependent contractions over a wide dose range. Somatostatin and enkephalin contracted the preparations only in the highest doses tested (10(-9) moles, 10(-8) moles). 5. Atropine did not reduce or abolish the response to any of the substances tested, indicating that their effects are not via cholinergic neurons, which innervate the smooth muscle. 6. Of the substances tested ATP, adenosine, VIP and neurotensin may be involved in the inhibitory vagal non-adrenergic, non-cholinergic innervation of the rainbow trout stomach.

Adenosine↗

VIP-, substance P-, gastrin/CCK-, bombesin-, somatostatin- and glucagon-like immunoreactivities in the gut of the rainbow trout, Salmo gairdneri.

The presence of peptides in the gastrointestinal tract of the rainbow trout, Salmo gairdneri, was investigated immunocytochemically. VIP-like immunoreactivity was demonstrated in nerves in all layers of the stomach and the intestine, whereas substance P-like immunoreactivity was localized to endocrine cells, predominantly in the mucosa of the stomach, and to nerves mainly concentrated in the myenteric plexus throughout the gut. Endocrine cells reactive to gastrin/CCK antiserum were demonstrated in the intestinal mucosa, while no immunoreactivity was found in the stomach. Bombesin-immunoreactive and somatostatin-immunoreactive cells were localized in the stomach mucosa, and cells reactive to glucagon antiserum in the intestinal mucosa. Radioimmunoassay of stomach mucosa and muscle confirmed the presence of VIP-like and substance P-like immunoreactivity in these tissues, while gastrin/CCK-like immunoreactivity was low and bombesin-like immunoreactivity was insignificant. In conclusion, molecules resembling the mammalian brain-gut peptides may be involved in the neuronal and hormonal control of gut function in fish.

Animals↗

Neuropharmacology of adrenergic neurons in teleost fish.

Although this brief review is based on relatively few types of experiments in few species of teleosts, it is possible to summarize some points of interest regarding the similarities and differences in the mechanisms of adrenergic neurotransmission in fish compared to the higher vertebrates. 1. There is a substantial mixing of cranial autonomic ("parasympathetic") and spinal autonomic ("sympathetic") pathways in the cranial nerves. This close relationship between the two systems and the differences in the nature of the neurons of cranial origin (cholinergic, and non-adrenergic, non-cholinergic) and spinal origin (adrenergic, cholinergic and mixed "polynergic") gives a basis in fish also for a complex pattern of innervation of the various organs. 2. Adrenaline is the major transmitter substance in the adrenergic neurons of most teleosts studied, but there are exceptions within the same species. For instance, in the swimbladder mucosa of the cod, noradrenaline dominates, while adrenaline is the major catecholamine in most other organs innervated by adrenergic neurons. The reasons for the regional differences are not known and further studies of the rate of catecholamine turn-over in the adrenergic neurons of fish are clearly indicated. 3. Adrenoceptors of both the alpha- and the beta-type show great similarities with those of mammals. Some differences in the potencies of certain compounds (e.g., clonidine and methoxamine) exist and receptor binding studies should add valuable information about the adrenoceptors of teleosts. The existence of a subtype of beta-adrenoceptor (beta 2) has been proposed and further work is needed to confirm or deny the applicability of the beta 1/beta 2 adrenoceptor terminology in fish. 4. There appears to be some differences in the mode of action of the so called "indirectly acting amines", such as tyramine, between teleosts and mammals. While the uptake of tyramine into the nerve terminals in mammals appears to take place via the cocaine-sensitive neuronal uptake system which is also responsible for catecholamine uptake (uptake 1), tyramine uptake in cod neurons appears to be via a separate pathway. 5. Presynaptic supersensitivity of the type seen in mammals has also been demonstrated in teleost adrenergic neurons. Both denervation (chemical or surgical) and blockade of the neuronal uptake mechanism by cocaine or desipramine produce this type of supersensitivity, while post-synaptic supersensitivity has so far not been described in teleosts. The effects of removal of the uptake system shows that the uptake process may be as important in teleosts as in mammals in the removal of adrenergic transmitter from the synaptic cleft. 6. In the total picture of adrenergic functions in fish, the circulating catecholamines take a special role...

Adrenergic Fibers↗

Effect of ischaemic on the adrenergic neurons of the rat heart: a fluorescence histochemical and biochemical study.

Left coronary artery ligation was performed in pentobarbitone anaesthetised rats. Following 1/2 and 2 1/2 h of coronary artery occlusion or sham-operation the right and left ventricular myocardium and the interventricular septum were analysed for tissue content of catecholamines. In control rats and in rats with coronary artery ligation for various time periods (1/2, 2 1/2 and 5 h), the Hillarp-Falck fluorescence histochemical technique was used to visualise the catecholamines of the ventricular myocardium. The tissue noradrenaline content of the left ventricle was markedly reduced after 2 1/2 h of ischaemia while noradrenaline levels in the other parts of the ventricles were unaffected. The adrenergic innervation of the normal rat ventricles is described for the purpose of comparing the normal innervation picture with the appearance after ischaemia. A reduced catecholamine fluorescence was found mainly in the centre of the left ventricular free wall 30 min after coronary artery occlusion. After 2 1/2 and 5 h large areas of the ischaemic myocardium were found to be completely devoid of fluorescent terminals. The border zone between the areas of fluorescence disappearance and normally innervated myocardial tissue was generally quite sharp and occasionally terminals with a diffuse appearance were found in this zone. It is concluded that coronary artery ligation caused a time-dependent loss of noradrenaline from the adrenergic nerve terminals in the ischaemic myocardium. Catecholamine thus released may activate myocardial adrenoceptors and hence be related to increased ischaemic damage and ventricular arrhythmias.

Adrenergic Fibers↗

On the chromaffin system of the African lungfish, Protopterus aethiopicus.

The distribution of chromaffin tissue was studied in the African lungfish using Falck-Hillarp fluorescent histochemistry together with quantitative analysis of catecholamines in plasma and tissue extracts. Intensely fluorescent cells form chromaffin tissue in the wall of the atrium, the wall of the most anterior part of the left cardinal vein and the walls of the segmentally arranged intercostal arteries. The arrangement thus appears to be a combination of the situations in cyclostomes, elasmobranchs and teleosts. Adrenaline is present in larger quantities than noradrenaline in the intercostal arteries and the cardinal vein, while noradrenaline dominates in the atrium. During "stress" induced by physical disturbance of the animals, a strong increase in especially the noradrenaline concentration of the plasma was detected.

Animals↗

Adrenergic and cholinergic effects on the heart, the lung and the spleen of the African lungfish, Protopterus aethiopicus.

Effects of adrenergic and cholinergic drugs were studied on isolated preparations from the heart, the lung and the spleen of the African lungfish. In addition, a nerve-lung preparation was employed for the study of the autonomic nervous control of the lung. Falck-Hillarp fluorescent histochemistry was used in the search for adrenergic neurons in the sympathetic chain and tissues. The Protopterus lung received a cholinergic excitatory innervation via the pulmonary branches of the vagi. The presence of parasympathetic ganglia in the lung tissue is indicated. Adrenergic drugs, when producing a response, either contracted or relaxed lung strips. Spleen strips were contracted by cholinergic drugs acting on muscarinic receptors and, to a lesser extent, by adrenergic drugs. A strong negative inotropic effect was produced by carcachol on paced atrial but not ventricular strips, while adrenaline increased the contraction force in ventricular but not atrial strips. The sympathetic ganglion cells did not contain enough catecholamines to give off any visible fluorescence, nor was it possible to show any adrenergic nerve terminals in the tissues studied. It is concluded that the adrenergic control in the lungfish is mainly due to circulating catecholamines, rather than adrenergic nerve fibres, since concentrations of catecholamines in protopterus plasma are high enough to affect the spleen, lung and ventricle.

Adrenergic Fibers↗

Regulation of the heart of a teleost, Gadus morhua, by autonomic nerves and circulating catecholamines.

The cod heart regulation has been investigated by anatomical studies, fluorescent histochemistry, nerve stimulation and drug effects on the perfused heart and electrically paced strips. The effect on the heart of catecholamine release from the head kidney has been studied in a perfused head kidney and heart preparation. Branches of the vagi and the fused 1st and 2nd spinal nerves innervate the heart. Specifically fluorescent fibres were found in these nerve branches, in the ducts of Cuvier, all parts of the heart, bulbus arteriosus and the ventral aorta. Weakly autofluorescent ganglion cells surrounded by specifically fluorescent varicose fibres were present in the walls of the sinus venosus. Vagal stimulation caused bradycardia altered after atropine to tachycardia. Spinal nerve and sympathetic chain stimulation also induced tachycardia, as did provoked catecholamine release from the head kidney. The tachycardia could be blocked by propranolol. Atropine increased and propranolol decreased basic heart rate and contraction force. Adrenergic drugs accelerated and acetylcholine retarded the perfused heart. A positive inotropic effect was obtained with adrenergic drugs on isolated heart strips, while acetylcholine produced a negative inotropic effect on atrial but not ventricular strips. It is concluded from this study that the cod heart has an inhibitory cholinergic nerve supply via the vagi and an excitatory adrenergic supply via both the vagi and the first spinal nerves. Sympathetically controlled release of catecholamines from the chromaffin tissue in the head kidney may also play an important role in the heart regulation.

Acetylcholine↗