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H Ahlman

Publications and source records attributed to H Ahlman.

At least 145 records · Page 8Linked to original sources
PubMed1987

Vagal release of serotonin into gut lumen and portal circulation via separate control mechanisms.

The mechanisms controlling vagally induced serotonin-like immunoreactivity (5-HTLI) release into portal circulation and jejunal lumen were studied in individual cats. In control animals, electrical vagal nerve stimulation significantly enhanced both the endoluminal secretion rate of 5-HTLI and the release of 5-HTLI to the portal vein. The vagally induced release of 5-HTLI to the portal circulation was blocked by pretreatment with propranolol or phenoxybenzamine, or by prior removal of the superior cervical ganglia, but was not blocked by atropine or hexamethonium. On the contrary, the luminal secretion of 5-HTLI after vagal stimulation was not blocked by adrenoceptor blocking agents or ganglionectomy, but instead was inhibited by cholinoceptor antagonists. Thus, in the same experimental animal it was shown that vagally induced release of 5-HTLI to the portal circulation was mediated by adrenoceptor mechanisms, while the luminal release of 5-HTLI was regulated via cholinoceptors. Based on indirect estimations, the apical release of 5-HT seems to be qualitatively small in comparison with the release into the portal circulation.

Animals↗
PubMed1987

Adrenergic control of serotonin release from carcinoid tumor cells in vitro and in vivo.

Serotonin (5-HT)-producing human carcinoid tumors of midgut origin were transplanted to the anterior eye chamber of cyclosporine-treated rats. The release of 5-HT from in oculo transplants was studied after stimulation with adrenoceptor agonists applied locally to the eye. Chamber fluid was collected by micropuncture of the eye. 5-HT levels were determined by liquid chromatography with electrochemical detection. The release of 5-HT in cell suspensions of the same tumors was similarly studied after incubation with adrenoceptor agonists. In both experimental models activation of adrenoceptors caused release of 5-HT from carcinoid tumor cells. Individual variations in the type of response to adrenoceptor stimulation could be demonstrated for the different tumors. In two tumors there was good agreement between in vitro and in vivo findings with release of 5-HT at selective activation of beta-adrenoceptors with isoprenaline. In a third tumor there was a release of 5-HT at activation of alpha-adrenoceptors with norepinephrine in vitro. However, 5-HT release from this tumor in vivo was demonstrated at activation of beta-adrenoceptors. This finding may reflect different adrenoceptor populations on the tumor cell surface, each population activated to various degrees in the in vivo and in vitro situation.

Animals↗
PubMed1987

An improved immunocytochemical method for subcellular localization of serotonin in rat enterochromaffin cells.

Serotonin-like immunoreactivity (5-HT-LI) has been localized at the ultrastructural level in enterochromaffin (EC) cells of rat gastrointestinal tract. Ultra-thin sections of tissues embedded in epoxy resin were incubated with 5-HT antisera and antibody binding sites were visualized with protein A-gold. Three different antisera were compared and were shown to require different fixation regimens for optimal preservation of 5-HT-LI. For one antiserum, tissues fixed in glutaraldehyde and osmium tetroxide could be used to demonstrate 5-HT-LI in EC cells. Immunocytochemical localization of 5-HT can thus be performed with good ultrastructural preservation of tissues. Quantitative evaluation of the intracellular distribution of 5-HT-LI was performed on EC cells from antrum, duodenum, and proximal colon, fixed in glutaraldehyde only. In all three locations, the majority of the gold particles (90%) in EC cells were localized over the dense core of the secretory granules, while a minor fraction (10%) were localized in parts of the cytoplasm devoid of granules. In EC cells fixed in glutaraldehyde and post-fixed in osmium tetroxide, 5-HT-LI was reduced by about 85%, although intracellular distribution was essentially the same as in cells fixed in glutaraldehyde alone. The results indicate that 5-HT in EC cells is stored mainly in secretory granules, with a small fraction of 5-HT being localized outside the granules.

Animals↗
PubMed1987

The use of a long-acting somatostatin analogue in the treatment of advanced endocrine malignancies with gastrointestinal symptoms.

Four patients with advanced endocrine malignancies were treated with a somatostatin analogue (SMS 201-995) for palliation of hormone-induced symptoms during 3-6 months. Two had the carcinoid syndrome (one midgut and one foregut), one had medullary thyroid carcinoma and an ectopic ACTH syndrome, and one patient had a metastatic gastrinoma. The carcinoid patients had excellent symptomatic relief with a low dose of the drug, 50 micrograms subcutaneously twice daily, in one case despite progression of tumour disease and biochemical tumour markers. These findings indicate an action of the drug not only on hormonal release but also at peripheral sites. The patient with medullary thyroid carcinoma had relief of gastrointestinal symptoms when the drug dose was increased (100 micrograms twice daily). The levels of ACTH in peripheral blood were reduced, but not the calcitonin levels. The gastrinoma patient had undergone a major pancreatic resection (Whipple procedure) and was treated with omeprazole. SMS 201-995 reduced the peripheral gastrin levels acutely, but during the treatment fasting gastrin values increased, and the tumour growth progressed. Treatment was stopped owing to elevated fasting glucose level, increased steatorrhoea, and clinical attacks of cholangitis. Special attention is advocated for patients with major pancreatic resection and biliary reconstruction, who may be susceptible to physiological effects of somatostatin (or its analogues)--that is, impaired insulin release and decreased motility.

Adolescent↗
PubMed1986

Release of serotonin from human carcinoid tumor cells in vitro and grown in the anterior eye chamber of the rat.

Serotonin (5-HT)-producing human carcinoid tumors have been successfully transplanted to the anterior eye chamber of cyclosporine treated rats. Tumor transplants were rapidly vascularized and viable tumor cells could be demonstrated in transplants grown for 2 to 3 weeks in oculo. The release of 5-HT from carcinoid tumor cells grown in the anterior eye chamber and from tumor cells in suspension was studied after stimulation with various adrenoceptor agonists. A dose dependent release of 5-HT upon stimulation with isoprenaline was demonstrated for all viable carcinoid tumors in oculo. The isoprenaline-stimulated release of 5-HT from the tumor cells was further studied in vitro, and was efficiently antagonized by propranolol or nadolol, but not by phenoxybenzamine, indicating activation of beta-adrenoceptors on carcinoid tumor cells upon isoprenaline stimulation. Incubation of tumor cells with verapamil, a calcium channel inhibitor, also prevented the release of 5-HT upon isoprenaline stimulation. Thus, carcinoid tumors can be successfully transplanted to the anterior eye chamber of cyclosporine treated rats, offering new possibilities to study the pharmacologic and biologic features of this tumor. In the future, carcinoid tumors, as well as other endocrine tumors, may be grown in oculo in rats and receptor pharmacology and individual sensitivity to cytotoxic drugs can be studied, thus enabling optimal clinical treatment.

Aged↗
PubMed1986

Adrenoceptor modulated flow through the rabbit ampulloisthmic region studied in vivo and in vitro.

In adult rabbit does ovulation was induced by human choriongonadotropin (hCG) 48 hours before experiments. At laparotomy the oviducts were cannulated from the ovarian and uterine ends. In vivo as well as in vitro the patency of the isthmus was studied with low viscous fluid perfusion of the ampulloisthmic region in antegrade direction. Intraluminally applied norepinephrine (NE) or phenylephrine (PhE) caused dual changes in transisthmic flow; administration of a low dose increased the flow, while high doses decreased the flow in vivo. In vitro, application of PhE only induced a dose-dependent reduction of flow. The PhE-induced reduction of flow was prevented by pretreatment with phenoxybenzamine in vivo and in vitro, suggesting activation of an alpha-adrenoceptor mechanism. Intraluminal application of terbutaline (T) caused a dose-dependent increase of flow, which was most prominent in vivo. Such an increase of flow was prevented by blockade of beta-adrenoceptors with propranolol or by selective blockade of beta 2-adrenoceptors with IPS 399 both in vivo and in vitro, indicating activation of a beta 2-adrenoceptor mechanism. The biochemical and hormonal changes 48 hours after ovulation imply a role for the sympathetic transmitter NE in causing a contractile state of the ampulloisthmic region ("tube locking") for retention of ova prior to nidation in the uterine cavity. The isthmus would then hypothetically act as a sympathetically innervated smooth muscle sphincter. The present results demonstrate a constrictory response of this region to high-dose stimulation of alpha-adrenoceptors in support of such a hypothesis. However, it must be noted that this region also possesses a population of beta-adrenoceptors at this time interval, which may interfere with a constrictor mechanism via circulating epinephrine.

Animals↗
PubMed1986

Growth of human pheochromocytomas in the anterior eye chamber of the rat. A histochemical study on amine and peptide content of pheochromocytoma tumour cells.

Tissue pieces from seven benign human pheochromocytomas have been successfully transplanted to the anterior eye chamber of cyclosporin-treated rats. In vivo observations showed that 74-99% of the tumour transplants were vascularized within one to two days after transplantation. No increase in the size of the transplants was noted during the observation period (1-4 weeks). Tumour transplants grown in non-immunosuppressed rats were initially vascularized but rejection started to occur one week after transplantation. Histochemical analysis of tumour transplants grown in immunosuppressed rats demonstrated numerous tumour cells with strong catecholamine fluorescence, some of which formed long cell processes on the host iris. Immunocytochemical analysis of tumour transplants demonstrated positively labelled tumour cells after incubation with antisera against neuropeptide Y, enkephalin, vasoactive intestinal polypeptide, somatostatin, substance P, dopamine-beta-hydroxylase, tyrosine hydroxylase and serotonin. A similar histochemical and immunocytochemical pattern was observed in primary tumours but tumour cells sending out cell processes were observed less frequently. Human pheochromocytomas may thus be successfully grown in oculo in cyclosporin-treated rats. This may prove to be a suitable model for the study of storage and release of catecholamines and neuropeptides from pheochromocytoma tumour cells.

Adrenal Gland Neoplasms↗
PubMed1986

Verapamil and diarrhoea in the carcinoid syndrome--clinical and experimental observations on serotonin release.

A patient with the midgut carcinoid syndrome with severe diarrhoea and proven hypersecretion of serotonin (5-HT) was treated with low doses of verapamil perorally. During treatment the patient was completely relieved of diarrhoea but discrete facial flushing persisted during treatment. When treatment was cessated, diarrhoeas recurred. This patient underwent pentagastrin (PG) provocation repeatedly; during untreated conditions injection of PG released 5-HT, detectable in peripheral venous blood. Such release was abolished during verapamil treatment, but recurred after withdrawal of the drug. Surgical biopsies from this tumour were studied in two experimental models: cell suspensions and heterotransplants grown in the anterior eye-chamber of immunosuppressed rats. Release of 5-HT from the cell suspensions was elicited in a dose-dependent manner after stimulation with isoprenaline (IP) suggesting activation of beta-adrenoceptors on the tumour cells. Such release was reduced after pretreatment with verapamil indicating a calcium dependent mechanism. Intraocular tumour transplants also responded with release of 5-HT into the chamber fluid after conjunctival application of IP. However, pretreatment of the rats with verapamil significantly reduced the IP-stimulated release of 5-HT.

Aged↗
PubMed1986

Regional and selective changes in blood flow of the feline small intestine induced by endoluminal serotonin.

A physiological role for endoluminal serotonin (5-HT) was explored in in vivo experiments, where feline jejunal segments were endoluminally perfused with saline or a low concentration of 5-HT. The upper jejunal segment was initially perfused with saline, followed by 5-HT in saline, and finally perfused with saline alone. The lower jejunal segment served as a control with constant perfusion with saline. The regional blood flow to the small intestine was determined by the microsphere technique. Endoluminal perfusion with 5-HT caused a selective muscular hyperaemia of the experimental gut segment, which was normalised upon subsequent saline perfusion. The blood flow to the saline perfused control segment was unchanged. This was also the case for control tissues; that is, adjacent small intestinal regions and kidneys. The 5-HT-induced muscular hyperaemia was confined to the experimental gut segment and seems to be mediated by a local cholinergic neural mechanism, activated from the mucosa, since the hyperaemic response was prevented by muscarinic blockade or local anaesthesia applied to the luminal surface of the experimental segment. The vascular response does not seem to involve 5-HT2 receptors, since selective blockade of such receptors did not prevent 5-HT-induced hyperaemia.

Animals↗
PubMed1986

Studies on the mucosal hyperaemia of the feline small intestine observed at endoluminal perfusion with substance P.

Substance P-like immunoreactivity (SPLI) was found in the luminal contents of the feline small intestine. A physiological role for endoluminal substance P (SP) was explored in in vivo experiments, where feline jejunal segments were endoluminally perfused with saline or a low concentration of SP. A jejunal segment was initially perfused with saline, followed by SP in saline, and finally perfused with saline alone. The regional blood flow to the small intestine was determined by the microsphere technique. Endoluminal perfusion with SP caused a selective mucosal/submucosal hyperaemia of the experimental jejunum, which was normalized upon subsequent saline perfusion. Since neither acute vagotomy, local neural blockade (TTX, lidocaine), adrenergic blockade (phenoxybenzamine, propranolol), cholinergic blockade (hexamethonium, atropine), histamine - nor prostaglandin blockade - could antagonize the hyperaemic effects of luminally administered SP, it is suggested that this effect is directly paracrine in nature. Substance P may be released from SP nerves on physiological stimulation, that is, augmented vagal tone by a meal, and act at the effector cell, that is, vascular smooth muscle.

Adrenergic alpha-Antagonists↗
PubMed1986

Increase in blood serotonin levels in the hepatic venous outflow after intraportal tumour cell injection.

An important role of platelet-liberated serotonin (5-HT) for the hepatic lodgement of intraportally injected tumor cells was suggested in previous studies. In the present investigation the inferior caval vein was cannulated for determination of 5-HT levels in the hepatic venous outflow in association with tumour cell lodgement in the liver. A peak of 5-HT could be demonstrated in the inferior caval vein 15 min after intraportal tumour cell injection, indicating exposition of the liver to high local concentrations of 5-HT in excess of the metabolizing capacity of the liver, associated with tumour cell lodgement.

Animals↗
PubMed1985

Adrenergic control of serotonin release from a midgut carcinoid tumour.

A case of recurrent midgut carcinoid tumour with disseminated spread is described, in which the clinical diagnosis was supported by measurements of elevated basal serotonin (5-HT) levels in peripheral blood and increased 5-HT responses to pentagastrin provocation, despite normal urinary levels of 5-hydroxyindoleacetic acid. Preoperative diagnosis was obtained by concomitant determinations of 5-HT in mesenteric and hepatic veins. The carcinoid tumour was studied immunocytochemically using antisera to tyrosine hydroxylase and 5-HT. Neuroendocrine complexes between adrenergic nerve terminals and 5-HT-containing tumour cells could be demonstrated. 5-HT release from tumour cells in suspension was studied in vitro after incubation with adrenoceptor agonists or pentagastrin. Tissue pieces from the tumour were also transplanted into the anterior eye chamber of Sprague-Dawley rats, some of which were subjected to immunosuppression (Cyclosporin A 20 mg/kg s.c.). After 10 days in oculo the tumour transplants (with preserved immunocytochemical characteristics) were stimulated with adrenoceptor agonists. Tumour cells in suspension as well as tumour transplants released 5-HT upon adrenoceptor stimulation but no release was induced by pentagastrin. The pentagastrin test is suggested to cause release of 5-HT in carcinoid tumour patients via release of endogenous catecholamines, in turn activating adrenoreceptors on carcinoid tumour cells.

Adrenergic alpha-Agonists↗
PubMed1985

Subcellular localization of serotonin immunoreactivity in rat enterochromaffin cells.

Serotonin immunoreactive material was localized to rat enterochromaffin cells (EC cells) at the subcellular level using antibodies to serotonin (5-HT) raised in rabbits. Ultrathin sections from paraformaldehyde fixed plastic embedded tissues were directly labelled with the 5-HT antiserum, using the protein A-gold technique to visualize the immunoreaction. The 5-HT immunoreactivity (5-HT-IR) in the rat gastrointestinal mucosa was exclusively localized to epithelial EC cells with a low background over other epithelial non-enterochromaffin cells. Quantitative evaluation of the immunoreaction revealed that most of the 5-HT-IR in the cytoplasm of EC cells (60%) was located over the dense cores of the secretory granules. However, a significant part of the cytoplasmic 5-HT-IR (40%) was located outside the dense cores of the secretory granules which suggests that different forms of 5-HT storage may exist.

Animals↗
PubMed1985

On the nature of the contractile motor responses of the rat stomach elicited by serotonin or substance P in vitro.

SP or 5-HT elicited contractile motor responses from strip preparations of the rat antrum and pylorus, effects which were efficiently antagonized by blockade directed against each substance (SP-receptors: tachyphylaxis or a SP analogue; 5-HT2 receptors: ketanserin). Indirect effects of SP or 5-HT, i.e. causing the release of other spasmogens such as histamine (from mast cells) and prostaglandins, were ruled out in separate experiments using pyrilamine or indomethacin. When the contractile effects of SP or 5-HT motor responses were studied after TTX no inhibition was demonstrated indicating that the effects were mediated via muscle receptors. Both SP- and 5-HT-responses were partially antagonized by blockade of muscarinic or nicotinic receptors, even in the presence of TTX, in favour of interaction at the receptor level of the smooth muscle membrane. One exception was the SP-induced pyloric contraction, which was partially atropine-sensitive but resistant to hexamethonium. Interestingly, blockade of 5-HT2 receptors (ketanserin) reduced the contractile response to SP. These observations indicate an interaction between SP and 5-HT receptors at the smooth muscle membrane. However, SP and 5-HT added together did no facilitate the response. Therefore, the interaction of ketanserin with the SP response may rather be sterical than due to binding to a common receptor site. These findings may be of importance, since SP and 5-HT have recently been shown to coexist in gut neurons.

Animals↗
PubMed1985

The effect of truncal vagotomy on serotonin distribution in the rat gastrointestinal tract.

The 5-HT levels in biopsies from the rat gastrointestinal tract were measured by a sensitive liquid chromatography method with electrochemical detection. The highest levels were found in the gastroduodenal and cecal regions. Sham-operated controls were compared with rats subjected to combined truncal vagotomy and pyloroplasty or pyloroplasty alone 5 weeks after surgery. Significantly decreased 5-HT levels were demonstrated in animals subjected to vagotomy + pyloroplasty or to pyloroplasty alone, compared with sham-operated controls. In the upper gastrointestinal tract of vagotomized animals significantly decreased 5-HT levels were found when compared with animals subjected to pyloroplasty alone. However, anesthesia and surgery (sham operation) per se markedly increased 5-HT levels of the gut even 5 weeks postoperatively, when compared with acutely killed rats. The underlying mechanism is still obscure. However, vagotomy largely prevented this increase. Therefore, the importance of correct controls is emphasized, since previous investigations claim to have demonstrated increased 5-HT levels in vagotomized animals, when compared with nonoperated controls.

Animals↗