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E Ekblad

Publications and source records attributed to E Ekblad.

At least 37 records · Page 2Linked to original sources
PubMed1999

Structural, neuronal, and functional adaptive changes in atrophic rat ileum.

BACKGROUND: Inactivity of the gut leads to atrophic changes of which little is known. AIMS: To investigate structural, neuronal, and functional changes occurring in bypassed rat ileum. METHODS: Morphometry was used to characterise the atrophic changes. The numbers of enteric neurones, their expression of neurotransmitters, and the presence of interstitial cells of Cajal were studied using immunocytochemistry and in situ hybridisation. Motor activity was studied in vitro. RESULTS: Adaptive changes in bypassed ileum include atrophy and remodelling of the gut wall. The total numbers of submucous and myenteric neurones per unit length increased one and four weeks after bypass but were identical to sham operated intestine 10 weeks after bypass. Neurones expressing vasoactive intestinal peptide, neuropeptide Y, or pituitary adenylate cyclase activating peptide decreased gradually in number in bypassed ileum. Nitric oxide synthase expressing neurones were increased, particularly in the myenteric ganglia. No change in the frequency and distribution of interstitial cells of Cajal was noted. The contractile response elicited by electrical stimulation of sham operated ileum consisted of a fast cholinergic twitch followed by a slower non-adrenergic, non-cholinergic contraction. In the bypassed ileum an identical biphasic contraction was elicited; however, the entire response was non-adrenergic, non-cholinergic. The relaxatory response to electrical stimulation in sham operated ileum was nitric oxide mediated; after bypass it was non-nitrergic. CONCLUSIONS: Notable atrophic changes were seen in the rat ileum after bypass. The enteric nervous system reacted with neuronal cell death and plasticity in terms of release and expression of neurotransmitters.

Anastomosis, Surgical↗
PubMed1998

Expression of non-classical islet hormone-like peptides during the embryonic development of the pancreas.

Understanding of islet embryogenesis may prove to be key in the design of future therapies for diabetes directed at re-initiating islet growth, with the goal to replace and/or replenish the impaired beta-cell mass in the disease. In this context, studies of islet neurohormonal peptides, known to play a role in the local regulation of islet function, and their expression during islet embryogenesis are important. Here we review our studies on the embryonic islet expression of islet amyloid polypeptide (IAPP) and the PP-fold peptides pancreatic polypeptide (PP), peptide YY (PYY) and neuropeptide Y (NPY). IAPP, which is constitutively expressed in beta- and delta-cells in the adult rat, was found to occur in the assumed pluripotent islet progenitor cell, together with PYY, glucagon, and to a lesser extent with insulin. As development proceeds, the insulin/IAPP phenotype is segregated from that of PYY/glucagon; with the formation of islet-like structures, insulin/IAPP-expressing cells primarily occupy their central portions, while PYY/glucagon-expressing cells are found in their periphery. At the time of formation of islet-like structures, expression of NPY is induced in the insulin/IAPP-containing cells. Whereas NPY-expression ceases at birth, PYY is constitutively expressed in non-beta-cells in the mature rat. Expression of PP is induced just prior to birth in a separate population of islet cells, occasionally co-expressed with PYY. Although a clear role for these peptides during embryogenesis has not been identified, they conceivably could play a role in the control of insulin secretion, islet growth and islet blood flow.

Amyloid↗
PubMed1998

Pituitary adenylate cyclase activating polypeptide (PACAP) in the gastrointestinal tract of the rat: distribution and effects of capsaicin or denervation.

The expression of pituitary adenylate cyclase activating polypeptide (PACAP) was studied in the gastrointestinal tract (GI-tract) of normal rats using radioimmunoassay, chromatography, immunocytochemistry, and in situ hybridization. PACAP-38, PACAP-27, and PACAP-related peptide were demonstrated in all parts of the GI-tract, PACAP-38 being the predominant form confirmed by chromatography. PACAP-immunoreactive nerve fibers and nerve cell bodies were found in the myenteric ganglia throughout the GI-tract. PACAP-containing nerve cell bodies were also demonstrated in the submucous ganglia of the small and large intestine. The synthesis of PACAP in intrinsic neurons was confirmed by in situ hybridization. Double immunostaining showed that PACAP is present in calcitonin gene-related peptide-containing sensory nerve fibers as well as in vasoactive intestinal polypeptide (VIP)- or VIP/gastrin-releasing peptide (GRP)-containing (intramural) nerve fibers in the upper GI-tract and in anally projecting, intrinsic VIP-and VIP/nitric oxide syntase-containing nerve cell bodies and nerve fibers in the small and large intestine. Neonatal treatment with capsaicin significantly reduced the concentration of PACAP-38 in the esophagus, stomach, and colon. Extrinsic denervation decreased the PACAP-38 concentration in the stomach, while no change was observed in the small intestine. These results indicate that PACAP- immunoreactive nerve fibers in the GI-tract originate from both intrinsic (enteric) and extrinsic (presumably sensory) sources suggesting that PACAP may have diverse gastrointestinal functions.

Animals↗
PubMed1998

Gastric mucosal smooth muscles may explain oscillations in glandular pressure: role of vasoactive intestinal peptide.

BACKGROUND & AIMS: Oscillating (3-7 cycles/min) high pressures in gastric glands during acid secretion suggest the existence of rhythmically contracting mucosal muscles. The aim of this study was to study vasoactive intestinal peptide (VIP), an inhibitory neurotransmitter in the gastrointestinal tract, in relation to mucosal muscles, glandular pressure, and blood flow. METHODS: Rat, dog, and human mucosae were examined immunocytochemically for smooth muscle actin and VIP. Glandular pressure was measured using microelectrodes, red blood cell velocity (V[RBC]) was measured using a cross-correlation technique, and blood flow was measured using laser Doppler flowmetry in exposed gastric mucosa of thiobutabarbital sodium-anesthetized rats. RESULTS: Actin immunostaining showed muscle strands arising from muscularis mucosae, extending toward the gastric pits. VIP-immunoreactive nerve fibers were found in close relation to these muscles. VIP, administered intra-arterially close to the stomach (2 microg/kg bolus, followed by 10 microg x kg[-1] x h[-1]), significantly decreased glandular pressure from 18.2 +/- 1.6 to 8.9 +/- 1.6 mm Hg and almost eliminated the pressure oscillations. VIP infusion also abolished the oscillations in V(RBC) and significantly increased blood flow by approximately 35%. CONCLUSIONS: Contracting mucosal muscles may be responsible for oscillations in glandular pressure and possibly also in V(RBC). VIP probably relaxes these muscles.

Animals↗
PubMed1998

Functional and morphological examination of ganglionic and aganglionic distal gut from the lethal spotted mouse.

The aim of the study was to evaluate both morphologically and functionally the distal large intestine from the aganglionic lethal spotted (ls/ls) mutant mouse and their healthy litter mates. Immunohistochemically, the aganglionic murine distal large intestine showed an absence of nerve cell bodies, and a reduction or absence of nerve fibers displaying immunoreactivity (IR) for protein gene product (PGP), nitric oxide synthase (NOS), vasoactive intestinal peptide (VIP), substance P (SP), galanin and calcitonin gene-related peptide (CGRP), while in the ganglionic large intestine these neuronal populations were abundantly present throughout the gut wall. Pathological nerve trunks within the afflicted intestinal segment were found to harbour PGP- and neuropeptide Y (NPY)-IR nerve fibers. Smooth muscle specimens from the distal part of the murine distal large intestine were mounted as ring preparations in vitro and subjected to electrical field stimulation (EFS). EFS (4-20 Hz) caused a contraction in both ganglionic and aganglionic intestine. After pretreatment with atropine EFS (20 Hz) evoked a biphasic motor response, a relaxation followed by a contraction in control specimens, while no motor response was seen in aganglionic intestine. Addition of the NOS-inhibitor N-nitro-L-arginine methyl ester (L-NAME) caused per se a weak and transient contraction and reduced the amplitude of the EFS-induced relaxation in control intestine.

Animals↗
PubMed1998

Enteric neuronal plasticity and a reduced number of interstitial cells of Cajal in hypertrophic rat ileum.

BACKGROUND: Partial obstruction of the ileum causes a notable hypertrophy of smooth muscle cells and enteric neurones in the proximally located intestine. AIMS: To study the expression of neuromessengers in the hypertrophic ileum of rat as little is known about neuromessenger plasticity under these conditions. To investigate the presence of interstitial cells of Cajal (ICC) in hypertrophic ileum. METHODS: Ileal hypertrophy was induced by circumferential application of a strip of plastic film for 18-24 days. Immunocytochemistry, in situ hybridisation, nicotinamide adenine dinucleotide phosphate (NADPH) diaphorase histochemistry, and ethidium bromide staining were used to investigate the number of enteric neurones expressing neuropeptides and nitric oxide synthase, and the frequency of ICC. RESULTS: In the hypertrophic ileum several neuronal populations showed changes in their expression of neuromessengers. Myenteric neurones expressing vasoactive intestinal peptide (VIP), pituitary adenylate cyclase activating peptide, and galanin were notably increased in number. In submucous ganglia the number of VIP immunoreactive neurones decreased while those expressing VIP mRNA increased. NADPH diaphorase positive submucous neurones increased dramatically while the number of neuronal type nitric oxide synthase expressing ones was unchanged. The number of ICC decreased notably in hypertrophic ileum. CONCLUSION: Enteric neurones change their levels of expression of neuromessengers in hypertrophic ileum. ICC are also affected. The changes are presumably part of an adaptive response to the increased work load.

Animals↗
PubMed1997

The effects of axotomy and preganglionic denervation on the expression of pituitary adenylate cyclase activating peptide (PACAP), galanin and PACAP type 1 receptors in the rat superior cervical ganglion.

The effects of axotomy, chemical sympathectomy and preganglionic denervation on the expression of the neuropeptides, pituitary adenylate cyclase-activating peptide (PACAP), galanin (GAL), and the PACAP type 1 receptor in the rat superior cervical ganglion (SCG) were investigated by immunocytochemistry, in situ hybridization and receptor autoradiography. An antibody recognizing the rat vesicular acetylcholine transporter (VAChT) was used for the detection of preganglionic cholinergic fibers. In the normal SCG, PACAP-immunoreactivity (-IR) was present in numerous, basket-forming, preganglionic nerve fibers, while very few SCG neurons expressed PACAP. GAL-IR was restricted to occasional neurons, and a few nerve fibers, most of which were, in addition, PACAP-IR. PACAP type 1 receptors were expressed in all nerve cell bodies. Axotomy resulted in a rapid and prominent upregulation of PACAP in a large number of nerve cell bodies. There was a large increase also in GAL expression in many nerve cell bodies. In contrast, there was a marked decline in PACAP type 1 receptor expression. Chemical sympathectomy by administration of the catcholaminergic neurotoxin, 6-hydroxydopamine (6-OHDA), gave rise to similar changes. Preganglionic denervation led to the disappearance of PACAP- and VAChT-IR baskets and to the upregulation of PACAP and GAL expression in neurons located close to the entrance of the sympathetic chain, whereas PACAP type 1 receptor expression was not affected. PACAP and GAL were coexpressed in most neurons after axotomy and chemical sympathectomy. Taken together, these results indicate that disruption of target contact and/or the infliction of an injury to the axons of the sympathetic neurons, rather than the preganglionic output, regulates the expression of PACAP, GAL and the PACAP type 1 receptor.

Animals↗
PubMed1997

Distinct receptors mediate pituitary adenylate cyclase-activating peptide- and vasoactive intestinal peptide-induced relaxation of rat ileal longitudinal muscle.

Relaxant responses to pituitary adenylate cyclase-activating peptide (PACAP)-27, PACAP-38 and vasoactive intestinal peptide (VIP) were examined in rat ileal longitudinal muscle. PACAP-27 was much more potent than PACAP-38 and VIP, with PACAP-38 and VIP being equipotent. The relaxation induced by each of the peptides was unaffected by pretreatment with NG-nitro-L-arginine methyl ester (L-NAME) (10[-4] M), tetrodotoxin (10[-6] M) or atropine (10[-6] M). Pretreatment with apamin (10[-6] M) abolished the relaxations induced by PACAP-27, but not those induced by PACAP-38 or VIP. Pretreatment with neuropeptide Y (NPY) (10[-7] M) inhibited relaxations induced by VIP, but not those induced by PACAP-27 or PACAP-38. No cross-desensitization between PACAP-27 and VIP could be revealed. In conclusion, distinct receptors mediate PACAP- and VIP-induced relaxations of rat ileal longitudinal muscle. At least three different types of receptors may exist: (1) a PACAP-27 preferring receptor coupled to apamin sensitive Ca2+-dependent K+ channels, (2) a PACAP specific receptor activated by both PACAP-27 and PACAP-38 but not by VIP and (3) a VIP specific receptor regulated by NPY by yet unknown mechanisms.

Animals↗
PubMed1997

Developmental expression of NPY, PYY and PP in the rat pancreas and their coexistence with islet hormones.

It has been suggested that members of the neuropeptide Y (NPY) family of regulatory peptides [NPY, peptide YY (PYY) and pancreatic polypeptide (PP)] play an important role in the development of the endocrine pancreas. The development of rat endocrine pancreas from embryonic (E) day 12 until 30 days postpartum (P) was studied with emphasis on NPY, PYY and PP and their co-existence with insulin, glucagon and somatostatin using single and double immunostaining and in situ hybridization. Already at E12, PYY was detectable in small endocrine cell clusters and found to be co-localised with both insulin and glucagon, which at this stage occurred in the same cells. At E16 most of the insulin-immunoreactive (IR) cells were distinct from the glucagon/PYY-IR cells. Interestingly, at E16 NPY mRNA, and at E17 NPY immunoreactivity appeared in a few, scattered endocrine cells. Virtually all NPY-IR endocrine cells were insulin-producing beta cells. At E18 the endocrine cells started to form typical islets with centrally located insulin/NPY-IR cells surrounded by glucagon/PYY-IR cells. AT E20-E21, the vast majority of insulin-producing cells also expressed NPY. However, at birth (day 0) islet cell NPY mRNA was lacking. Postnatally the number and immunostaining intensity of NPY-IR islet cells rapidly declined, being non-detectable at P5. Cells containing PP immunoreactivity and PP mRNA were first detected at E21. The adult pattern of islet peptide distribution, with NPY confined to neuronal elements. PYY and PP exclusively in endocrine cells, was established at P5. The beta cell expression of NPY during the latter part of embryogenesis coincides with the prepartal glucocorticoid surge and with rapid islet cell replication and differentiation. This is compatible with steroid induction of NPY expression and with a role for NPY in the maturation of beta cells and their hormone release, which occurs in the immediate neonatal period.

Animals↗
PubMed1997

PreproVIP-derived peptides in the human female genital tract: expression and biological function.

The aim of the study was to elucidate the localization, distribution, colocalization and biological effect of preproVIP-derived peptides in the human female genital tract. Radioimmunoassays applying antisera against the five functional domains of the VIP precursor in combination with immunohistochemistry were used. The effect of preproVIP 22-79, preproVIP 111-122 and preproVIP 156-170 on genital smooth muscle activity in the Fallopian tube was investigated in vitro and compared to that of VIP. All the preproVIP-derived peptides were expressed throughout the genital tract in neuronal elements closely related to the epithelial lining, perivascular tissue and non-vascular smooth muscle. Colocalization of the peptides was evidenced by double immunostaining. In contrast to VIP, preproVIP 22-79, preproVIP 111-122 and preproVIP 156-170 did not cause a significant inhibition of smooth muscle activity. The findings indicate that tissue-specific differences in post-translational processing of preproVIP exist in the female genital tract.

Adult↗
PubMed1997

Islet amyloid polypeptide in the gut and pancreas: localization, ontogeny and gut motility effects.

The occurrence of islet amyloid polypeptide (IAPP) in the gut and pancreas of several species and during ontogeny of the rat, was studied using immunocytochemistry. Effects of IAPP on rat ileal smooth muscle were assessed in vitro. Islets of most, but not all, species examined, displayed IAPP in insulin cells and, in some species, also in somatostatin- and peptide YY (PYY)-containing cells. In the gut, expression of IAPP varied among species; when present, IAPP was most abundant in the proximal part and co-localized with somatostatin, PYY, gastrin/cholecystokinin, enteroglucagon or serotonin. IAPP was first demonstrated at embryonic day 12 and 16 in islet and gastrointestinal endocrine cells, respectively. IAPP relaxed gut muscle and reduced electrical field stimulation-evoked contractions, presumably by inhibiting acetylcholine release. Thus, IAPP expression in islets is consistent with an important role for IAPP in fuel metabolism; the gastrointestinal expression and motor effects of IAPP suggest that IAPP may modulate gastrointestinal function.

Amyloid↗
PubMed1997

Supersensitivity in rat micro-arteries after short-term denervation.

Contractile responses to phenylephrine and high-K+ were investigated in vitro in microvascular preparations from the rat medial plantar artery, a branch from the saphenous artery, obtained after short-term denervation in vivo. Two groups of animals were studied: (1) animals undergoing surgical resection of the saphenous nerve, and (2) animals undergoing surgical resection of both the sciatic and saphenous nerves. The animals were operated on one side only. Microvascular preparations (diameter about 325 microns) were obtained 10 days after surgery. Vessels from the non-operated side served as controls. Immunocytochemistry showed a decreased number of both neuropeptide Y (NPY) and calcitonin gene-related peptide (CGRP) immunoreactive nerve fibres in vessels after resection of the saphenous nerve only. Resection of both the saphenous and the sciatic nerve caused a complete loss of immunoreactive nerve fibres. Mechanical measurements were performed using a wire myograph. In vessels subjected to resection of the saphenous nerve the sensitivity to phenylephrine was similar to controls. Vessels denervated by resection of both the saphenous and sciatic nerves showed significant increases in phenylephrine and potassium sensitivity. When depolarized in high-K+ solution the denervated vessels showed an increased sensitivity to extracellular Ca2+. The results show that complete short-term denervation of the rat medial plantar artery in vivo causes a pronounced supersensitivity in the vascular smooth muscle. The supersensitivity appears not to be restricted to the sympathetic alpha-receptors but also associated with changes in the cellular excitation-contraction coupling. Such altered reactivity of the vascular smooth muscle may contribute to vascular disturbances observed in vivo after nerve damage or surgical denervation.

Adrenergic alpha-Agonists↗
PubMed1997

Motor responses in rat ileum evoked by nitric oxide donors vs. field stimulation: modulation by pituitary adenylate cyclase-activating peptide, forskolin and guanylate cyclase inhibitors.

This study examines nitric oxide (NO) mediated effects on longitudinal muscle with adherent myenteric ganglia from rat ileum in vitro using NO donors and electrical field stimulation. Electrical field stimulation (20 Hz) caused a biphasic response-a relaxation followed by a contraction. NG-nitro-L-arginine methyl ester almost totally abolished the relaxation and L-arginine restored it. The contraction was unaffected. The NO donors sodium-nitroso-N-acetylpenicillamine (SNAP) and sodium-nitroprusside also induced a biphasic response, a contraction followed by relaxation. Relaxations mediated by neuronally released NO were not blocked by methylene blue or 1H-[1,2,4]oxadiazolo[4,3-a]-quinoxalin-1-one suggesting that they are independent of a rise in intracellular cyclic guanylate cyclase. Their amplitude was unaffected by forskolin. The relaxations evoked by NO (or a NO-related substance) liberated from SNAP were blocked by methylene blue or 1H-[1,2,4]oxadiazolo[4,3-a]-quinoxalin-1-one indicating a cyclic guanylate cyclase-dependent mechanism of action. Pituitary adenylate cyclase-activating peptide and forskolin, but not vasoactive intestinal peptide or neuropeptide Y, caused a marked leftward shift of the concentration-response curve of the SNAP-induced relaxation. The contractions induced by SNAP were blocked by methylene blue and 1H-[1,2,4]oxadiazolo[4,3-a]-quinoxalin-1-one and thus, cyclic guanylate cyclase dependent. The SNAP-induced contractions were abolished by pituitary adenylate cyclase-activating peptide and forskolin, but unaffected by vasoactive intestinal peptide or NPY. In conclusion, motor responses evoked by NO released from NO donors vs. neuronally released NO reveals different mechanisms of action.

Animals↗
PubMed1996

Vasoactive intestinal peptide expression in enteric neurons is upregulated by both colchicine and axotomy.

Axotomy is known to induce changes in neuropeptide expression in several types of neurons. Colchicine blocks the axonal transport and may mimic axotomy. The effects of colchicine-treatment and axotomy (local nerve crush by clamping of the gut) on enteric neurons expressing vasoactive intestinal peptide, neuropeptide Y and nitric oxide synthase were studied in rat small intestine by immunocytochemistry and in situ hybridization. Colchicine treatment significantly increased the number of submucous and myenteric neurons expressing vasoactive intestinal peptide and its mRNA. In contrast, an increase in the number of neuropeptide Y or nitric oxide synthase expressing neurons could not be detected. Axotomy markedly increased the number of myenteric vasoactive intestinal peptide-immunoreactive neurons in the segment located orally to the lesion, but not in the segment anally to the lesion, whereas that of nitric oxide synthase and neuropeptide Y expressing neurons was not affected. Double immunostaining revealed that the myenteric neurons containing nitric oxide synthase were induced by colchicine and axotomy to express vasoactive intestinal peptide. The present data indicate that colchicine and axotomy may induce marked changes in the neuropeptide expression of enteric neurons.

Animals↗
PubMed1996

Expression of prepro-VIP derived peptides in the gastrointestinal tract of normal, hypothyroid and hyperthyroid rats.

Vasoactive intestinal polypeptide (VIP) is a widespread neuropeptide involved in the autonomic nervous control of smooth muscle activity, blood flow and secretion. To study the biosynthetic processing of the VIP precursor in the gut of normal, hypo- and hyperthyroid rats we used antisera against the five functional domains of the precursor molecule, prepro-VIP 22-79, peptide histidine isoleucine (PHI), prepro-VIP 111-122, VIP and prepro-VIP 156-170, to quantify and characterize VIP precursor peptides by radioimmunoassay and chromatography and examine their cellular localization and co-localization by immunohistochemistry. All five peptides were expressed in the gut but not in equimolar amounts as expected from the structure of the VIP precursor. A high concentration of PHV, the C-terminally extended form of PHI which includes prepro-VIP 111-122, was found in the small intestine. Immunohistochemically the prepro-VIP derived peptides were shown to coexist in neuronal elements. Changes in thyroid hormone status induced moderate changes in peptide expression in the gut, the most prominent being a 2-fold increase in all prepro-VIP derived peptides in the gastric fundus of hypothyroid rats. The findings indicate that differences in the post-translational processing of prepro-VIP exist in neurons of the rat gut and that hypo- and hyperthyroidism induce differential changes in peptide expression.

Animals↗
PubMed1996

Distribution of neuropeptide-, tyrosine hydroxylase- and nitric oxide synthase containing nerve fibers in the external urethral sphincter of the rat.

The occurrence and distribution of adrenergic, peptidergic and nitrergic nerve fibers were investigated within the part of the rat urethra that corresponds to the external urethral sphincteric mechanism. At this level, the urethral wall was found to be composed of the following layers: mucosa/urothelium, lamina propria, smooth muscle, mixed smooth and striated muscle and striated muscle. Nerve fibers containing immunoreactivity against either nitric oxide synthase (NOS) or any of the following peptides were visualised in various amounts in all three muscle layers of rats of both sexes: neuropeptide Y (NPY), vasoactive intestinal polypeptide (VIP), calcitonin gene related peptide (CGRP), substance P (SP), cholecystokinin (CCK), gastrin releasing peptide (GRP) and pituitary adenylate cyclase-activating peptide. (PACAP) Tyrosine hydroxylase (TH), marker for nonadrenergic nerves, was only found in nerve fibers of the smooth and mixed muscle layers, while enkephalin 8 (ENK-8) was only found in the striated muscle layer. The great number of putative neuromessengers and different nerve fiber populations suggest a complex innervation pattern of the sphincter area.

Animals↗