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H Ahlman

Publications and source records attributed to H Ahlman.

At least 181 records · Page 10Linked to original sources

Vagal mechanisms controlling serotonin release from the gastrointestinal tract and pyloric motor function.

This chapter focuses on investigations of two mechanisms controlled by the vagal nerve; serotonin (5-HT) release from the small intestine and pyloric motor function. Morphological, physiological, pharmacological and biochemical methods were combined in these studies. 5-HT is mainly stored in enterochromaffin cells (EC), but is present also in mast cells and nerve terminals of the gut, as observed by immunocytochemistry. Vagal nerve stimulation causes a release of 5-HT from EC to the portal circulation and to the gut lumen. Morphological evidence for the endoluminal release of 5-HT was obtained by autoradiography and immunofluorescence. The 5-HT release from EC is mediated by a beta-adrenoceptor mechanism via sympathetic adrenergic fibers in the vagal nerve, originating from sympathetic ganglia, e.g. the superior cervical ganglion. This vagal adrenergic pathway was studied by fluorescence microscopy and retrograde tracing of horseradish peroxidase. The vagal peptidergic (nonadrenergic, noncholinergic) control of pyloric motor function was studied in chloralosed cats by means of an in vivo model, where changes of an applied flow of body-warm saline through the pylorus were recorded. Also, gastric volume changes were monitored. By means of immunofluorescence the presence of VIP-, enkephalin (ENK)- and substance P (SP)-like immunoreactivity was demonstrated in pyloric neurons and in the vagal nerve. Physiological evidence for a vagal VIPergic relaxatory mechanism was obtained, while ENK-neurons seem to mediate the vagally induced pyloric contraction, prevented by naloxone pretreatment. SP may mediate part of the vagally induced pyloric and gastric contraction, the latter probably via axon collaterals on final cholinergic neurons. ENKergic and SPergic vagal contractile mechanisms seem to be additive for the pylorus.

Animals↗

Different modes of action of substance P in the motor control of the feline stomach and pylorus.

In an experimental in vivo model to study gastropyloric motility in the cat a contraction of the stomach and the pyloric sphincter was regularly obtained in animals subjected to electrical vagal nerve stimulation or local intraarterial (i.a.) injection of substance P (SP). Much more infrequently contractile motor responses were recorded at splanchnic nerve stimulation. The contractile effects of SP were sensitive to atropine or local infusion of a SP analogue, (D-Pro2,D-Trp7,9)-SP, indicating that SP activated a final common cholinergic neuron in both stomach and pylorus. However, there seemed to be separate transmission mechanisms in these two regions based on the results of the physiological studies. The vagally induced pyloric contraction was noncholinergic, nonadrenergic, but sensitive to ganglionic blockade (hexamethonium) or the SP analogue, indicating involvement of SP in a peptidergic pathway to the sphincter. The infrequent splanchnically induced pyloric contraction was sensitive to atropine, the SP analogue or ganglionic blockade (hexamethonium) in favour of SP acting on a final cholinergic neuron in this system. On the other hand the gastric contraction, obtained at either extrinsic nerve stimulations or local i.a. injection of SP, was sensitive to atropine or the SP analogue but hexamethonium resistant. These findings suggest antidromic activation of SP-containing axon collaterals of the extrinsic nerves terminating on cholinergic neurons of the gastric wall. When afferent C-fibres of the vagal nerve were selectively activated by local heating, pyloric contraction and gastric relaxation were obtained via vago-vagal reflexes. After cervical vagotomy heating of the distal end of the vagal nerve elicited a gastric contraction, previously demonstrated to be atropine sensitive and hexamethonium resistant, but no pyloric motor response. This suggests that the antidromic activation mechanism was present only in the stomach, not in the pylorus.

Animals↗

Suggestive evidence for a direct innervation of mucosal mast cells.

Mast cells are often observed near nerves and functional evidence suggests an innervation of these cells. In the present ultrastructural study, nerve terminals containing many small clear vesicles and a few large vesicles with dense matrix were observed in direct contact with the plasma membrane of mucosal mast cells in the rat ileum, strongly suggestive of a direct innervation.

Animals↗

Effects of intraluminal administration of adrenoceptor agonists on transisthmic flow in the rabbit oviduct.

By perfusing the isthmic segment of the rabbit oviduct in vivo at low hydrostatic pressures with Ringer's solution (+38 degrees C), the resistance of the isthmic segment could be measured quantitatively using a drop-recording system. Transisthmic flow, from mid-tube to the uterine end, was thus studied in 45 animals, 48 h after human chorionic gonadotropin (hCG) injection. Stimulation of alpha-adrenoceptors by administration of norepinephrine or phenylephrine to the perfusate resulted in an immediate reduction or cessation of the basal flow. The duration of this effect varied dose-dependently. The administration of beta-adrenoceptor agonists (isoprenaline, prenalterol or terbutaline) markedly increased transisthmic flow. The beta 2-adrenoceptor agonist terbutaline was considerably more potent than the other beta-agonists. Thus, it seems that the isthmic contraction caused by adrenergic luminal stimulation is mediated via alpha-adrenoceptors, while the isthmic dilation is mediated via beta-adrenoceptors, mainly of the beta 2-type.

Animals↗

5-Hydroxytryptamine and cholera secretion: a histochemical and physiological study in cats.

The effect of cholera toxin on the content of 5-hydroxytryptamine (5-HT) in the enterochromaffin cells of the cat small intestine was estimated by cytofluorimetry of individual enterochromaffin cells at varying times after exposing the intestinal mucosa to the toxin. The observed changes in 5-HT levels in the enterochromaffin cells were correlated with the simultaneously measured rate of net fluid transport across the intestinal epithelium. Intestinal segments exposed to cholera toxin showed a statistically significant decrease in 5-HT levels of enterochromaffin cells compared with segments exposed to heat-inactivated cholera toxin. A good correlation (r = 0.73) was found between relative 5-HT fluorescence in enterochromaffin cells and net fluid transport across the intestinal epithelium. Thus, a diminished 5-HT content was associated with a decreased rate of fluid absorption or an increased rate of secretion. A hypothesis is presented for explaining the possible role of the enterochromaffin cells in the pathophysiology of cholera secretion.

Animals↗

Ultrastructural observations in the rat ileal mucosa of possible epithelial "taste cells" and submucosal sensory neurons.

Electronmicroscopical studies of the rat ileum have demonstrated the presence of submucosal neuronlike cells located just under the basal lamina of intestinal crypts. These cells had dendrite-like processes and frequently made contacts with adjacent submucosal nerve terminals. Furthermore, within the mucosa epithelial "clear' cells with apical cytoplasmic processes into the gut lumen and basal cytoplasmic processes extending underneath adjacent epithelial cells were demonstrated. The "clear' cells were devoid of secretory granules, as e.g. endocrine cells, and had a morphological resemblance to taste cells. Occasionally the "clear' cells made contacts with submucosal nerve terminals. The possibility that the "clear' cells and submucosal neuronlike cells represent a receptive function within the intestine is discussed.

Animals↗

Evidence for a non-classical splanchnic neural control of the feline pylorus.

Electrical stimulation of the divided splanchnic nerves proximal to the celiac ganglion in chloralosed cats induced a dilation of the pylorus in the majority of animals. However, in some cats a pure contractile motor response or a biphasic motor response (contraction followed by dilation) was elicited suggesting that the splanchnic nerves convey excitatory fibres to the pylorus as well. The pyloric and gastric contraction at such stimulation was sensitive to atropine, while the pyloric dilation was not sensitive to cholinergic, adrenergic or ganglionic blocking agents in contrast to the adrenergic gastric dilation. Since the splanchnic nerve and the pyloric wall contain numerous neuropeptides, these substances might be involved in a nonclassical neurotransmission of the splanchnic motor responses of the pylorus.

Animals↗

The cellular uptake of 5-hydroxytryptamine in the rat lung in vivo--a histochemical study.

The cellular uptake of 5-hydroxytryptamine (5-HT, serotonin) in the rat lung was studied in vivo after bolus injection of the amine (1 mg/100 g b.w.i.v.). The cells responsible for the 5-HT uptake were visualized by fluorescence microscopy according to the Hillarp-Falck technique and further identified as mast cells by Astra Blau staining. The quantitative aspects of the 5-HT uptake were studied by a specific cytofluorimetric method. A significantly increased intracellular content of 5-HT was found in interstitial pulmonary mast cells 1 min after injection. No 5-HT uptake was demonstrated within epithelial cells of the bronchiolar mucosa or within the pulmonary vascular endothelial cells; not even in animals pretreated with monoamine oxidase inhibitor. This finding is in contrast to the endothelial uptake earlier demonstrated by autoradiography in artificially perfused lungs. One explanation for this discrepancy may be a rapid transport of the amine across the vast endothelial area in the lung in vivo resulting in low 5-HT concentrations within the endothelium, not detectable by fluorescence microscopy. After endothelial passage the amine was rapidly taken up and stored in interstitial mast cells, which normally have the amine handling properties.

Animals↗

Effect of cervical and thoracic vagal stimulation on luminal serotonin release and regional blood flow in cats.

In acute experiments on 14 cats, the transected vagus nerves were stimulated at two levels (10 V, 5 ms, 10 Hz, 10 mA, 15 min). Fifteen-centimeter proximal jejunal segments were perfused with saline (1.0 ml/min). Basal luminal immunoreactive serotonin secretion averaged 206 +/- 67 ng/5 min. After stimulation of the vagus nerves, there was an immediate two- to threefold increase in the rate of secretion of immunoreactive serotonin into the lumen. There were no significant differences in the stimulated secretory rates that resulted from stimulation at the cervical or thoracic levels. Shortly after cessation of vagal stimulation, immunoreactive serotonin secretory rates returned to basal. Vagal nerve stimulation did not result in any change in peripheral or portal venous blood concentrations of serotonin. In 12 additional cats, the effects of stimulation of the vagus nerves at the cervical and thoracic levels on regional blood flow, as determined using the microsphere technique, were compared. Cervical vagal stimulation resulted in hypotension, bradycardia, decreased perfusion of the heart, kidney, and small and large bowels, but preservation of the perfusion of the fundus and antrum. In contrast, stimulation of the transected nerves in the chest stimulated gastric blood flow but did not alter either flow to other viscera or central hemodynamics.

Animals↗

Release of immunoreactive serotonin into the lumen of the feline gut in response to vagal nerve stimulation.

Immunoreactive serotonin was detected in the lumen of the proximal jejunum of food-deprived cats. During perfusion of this intestinal segment in vivo, there was a constant basal rate of intraluminal secretion of this amine. The rate of secretion was significantly increased during efferent electrical stimulation of the cut cervical vagal nerves. This stimulatory effect was not altered after bilateral adrenalectomy was performed in the same animals. A synchronous release of substance P into the gut lumen was also demonstrated during vagal stimulation. During the period of increased intraluminal secretion of immunoreactive serotonin, there was no demonstrable change in the portal or systemic blood levels of this amine.

Adrenalectomy↗

Engulfment of erythrocytes by intestinocytes of the rat ileum.

The innervation of ileal mucosa of normal, unanaesthetized male Wistar rats was investigated electronmicroscopically. The presence of RBC inside intestinocytes was a secondary, but frequent observation in 4 of 20 rats. No sign of hemorrhage or trauma of the tissue was noted, and the rats had not been exposed to any known toxic agent. The study demonstrates that also intestinocytes have the capacity to engulf RBC, as many other types of epithelial cells. However, previous demonstration of RBC phagocytosis of epithelia was performed in tissues where hemorrhage had occurred for various reasons. In contrast, the rats of the present study were considered normal, although the influence of unknown agents cannot be ruled out.

Animals↗

On the presence of serotonin in the gut lumen and possible release mechanisms.

The possible presence of a luminal release of serotonin (5-HT) from gut enterochromaffin cells (EC) of the rat, was studied after the injection of the tritiated 5-HT precursor 5-hydroxytryptophan (3H]-5-HTP by electron microscopic autoradiography. The uptake of 5-HTP into gut epithelial cells was also studied by fluorescence histochemistry according to the Hillarp-Falck technique at the same post-injection interval as in the autoradiography experiments. 3 h after the injections of 5-HTP (100 mg/kg i.v.) the fluorescence intensity of EC was increased and numerous, probably enteroendocrine, cells had an increased yellow tryptamine induced fluorescence due to an uptake of 5-HTP and probably decarboxylation to 5-HT. However, the labelled precursor [3H]-5-HTP was taken up not only into granules of enteroendocrine cells but also incorporated into the cytoplasm and nucleus of nonendocrine cells when studied by autoradiography. After 10 min of efferent electrical stimulation of the vagal nerve much of the label was found in the gut lumen suggesting a release of the amine. The hypothesis of a luminal release of 5-HT was further corroborated in starved cats, where considerable amounts of 5-HT were detected by fluorimetric assays in the lumen of isolated jejunal loops under resting conditions. The experiments demonstrate that :(i) 5-HTP is taken up not only into typical EC but also into other enteroendocrine cells, and most probably decarboxylated to 5-HT. (ii) Also intestinocytes take up [3H]-5-HTP and incorporate the amino acid into peptides to a certain extent. (iii) Following vagal nerve stimulation labelled material, probably 5-HT, is secreted into the gut lumen. (iv) 5-HT normally occurs in the gut lumen.

5-Hydroxytryptophan↗

In vivo studies of the motility of the isthmic segment in the perfused rabbit oviduct.

The motility of the isthmic segment of the rabbit oviduct was studied in vivo using a perfusion model. The transisthmic flow of saline (38 degrees) was recorded at constant inflow pressures uni- or bilaterally. In untreated control animals there was a high resistance to flow within the isthmic segment. 12, 24, 48 and 72 h after induced ovulation by i.v. injection of human choriongonadotropin (HCG; 50 IU) the resistance gradually declined. No synchronous spontaneous motility pattern was recorded from the oviducts of any animal. When adrenergic agonists were administered 48 h after HCG, either intraluminally or intravenously, flow ceased after the alpha-adrenoceptor agonists noradrenaline (2-50 micrometers) or phenylephrine (2-10 micrograms), while an increased flow was recorded after the beta-adrenoceptor agonist isoprenaline (5-100 micrograms). The duration of the motor effects varied dose-dependently. Therefore it seems as if the motility of the isthmic segment is under adrenergic control, at least 48 h after HCG, with contractions caused by alpha-adrenoceptor stimulation and dilations caused by beta-adrenoceptor stimulation. The perfusion model used appears to be suitable for studying the adrenergic control of the isthmic segment after appropriate pretreatment with HCG.

Adrenergic alpha-Agonists↗

Clinically diagnosed small intestinal tumors in an urban Swedish area. A 10-year survey.

The clinical records of 55 patients with small intestinal tumors (SIT) in Gothenburg under a 10-year period (1968-1977) were reviewed. All patients except three had surgical treatment. Histopathologically 12 patients had benign lesions (most commonly leiomyomas), while 39 patients had malignant lesions. Among SIT with malignant potential carcinoids were most common followed by sarcomas and carcinomas. SIT usually presented with either obstruction or intestinal hemorrhage. The duration of symptoms was much shorter for sarcomas and carcinomas than for carcinoids or benign tumors. SIT were most frequent in the distal part of the small intestine, where especially carcinoids and sarcomas dominated. The clinical diagnosis was mainly based on X-ray examinations; however with a low accuracy for lesions distal to the duodenum. In 71% of the SIT cases resection for cure was possible to perform.

Adenocarcinoma↗