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Biomedical subjects

R Håkanson

Publications and source records attributed to R Håkanson.

At least 55 records · Page 3Linked to original sources
PubMed1999

Gastrectomy induces impaired insulin and glucagon secretion: evidence for a gastro-insular axis in mice.

1. Mice were subjected to gastrectomy (GX) or food deprivation (24 h). The release of insulin and glucagon in response to different secretagogues was monitored in vivo and in isolated islets 3-4 weeks after surgery. 2. GX animals responded to glucose with an impaired glucose tolerance and a poor increase in plasma insulin. Islets from GX or food-deprived mice displayed impaired insulin release to high glucose and enhanced glucagon release at low glucose. 3. After GX the insulinogenic index, Delta insulin (microU ml-1)/Delta glucose (mg ml-1), was suppressed by 65% after oral glucose and by 59% after i.v. glucose. The integrated insulin response after oral glucose was reduced by 90% in GX mice. After i.v. glucose the reduction was 67%. 4. Carbachol-induced insulin release in vivo was reduced after food deprivation and exaggerated after GX. Carbachol-stimulated glucagon secretion was suppressed after GX and after food deprivation. A similar pattern was found in vitro. 5. Cyclic AMP activation (by the phosphodiesterase inhibitor isobutylmethylxanthine or the adenylate cyclase stimulator forskolin) induced a greater insulin response in GX or food-deprived mice than in sham-operated, fed mice. A similar pattern was found in vitro. The glucagon response was enhanced in vitro but not in vivo. 6. Crude extracts of rat oxyntic mucosa enhanced basal as well as glucose-induced insulin release from isolated islets, whereas glucagon release was markedly inhibited. The effects were dose dependent, the inhibition of glucagon release being achieved at lower concentrations than the potentiation of glucose-induced insulin release. The active principle was inactivated by incubation with trypsin or leucine aminopeptidase. 7. The data suggest that a circulating agent, probably a peptide, from gastric oxyntic mucosa stimulates glucose-induced insulin secretion. It also suppresses glucagon secretion. The GX-evoked impairment of the insulin (and glucagon) response to glucose is partly compensated for by an enhanced insulin response to cholinergic and/or cyclic AMP activation.

1-Methyl-3-isobutylxanthine↗
PubMed1999

Effects of reserpine on ECL-cell ultrastructure and histamine compartmentalization in the rat stomach.

The histamine-storing ECL cells in the stomach play a key role in the control of acid secretion. They contain granules, secretory vesicles and microvesicles, and sustained gastrin stimulation results in the additional formation of vacuoles and lipofuscin bodies. The cells are rich in the vesicle monoamine transporter type-2 (VMAT-2), which can be inhibited by reserpine. The present study examines the effect of reserpine on ECL-cell ultrastructure and histamine compartmentalization. Rats received reserpine and/or gastrin. Reserpine was given twice by the intraperitoneal route (25 mg/kg once daily). Gastrin-17 was given by subcutaneous infusion (5 nmol/kg/h), starting at the time of the first reserpine injection and continuing for 4 days when the rats were killed. At this stage, histamine in the oxyntic mucosa was unaffected by reserpine but elevated by gastrin. Immunocytochemical analysis (confocal microscopy) showed ECL-cell histamine in control and gastrin-treated rats to be localized in cytoplasmic organelles (e.g., secretory vesicles). After treatment with reserpine alone or reserpine+gastrin, ECL-cell histamine occurred mainly in the cytosol. Planimetric analysis (electron microscopy) of ECL cells showed reserpine to increase the number, size and volume density of the granules and to reduce the size and volume density of the secretory vesicles. Gastrin reduced the number and volume density of granules and secretory vesicles, increased the number and volume density of microvesicles and caused vacuoles and lipofuscin bodies to appear. Reserpine+gastrin increased the number, volume density and size of the granules. Reserpine prevented the effects of gastrin on secretory vesicles, vacuoles and microvesicles, but did not prevent the development of lipofuscin. Our findings are in line with the views: (1) that preformed cytosolic histamine is taken up by granules/secretory vesicles via VMAT-2, that histamine is instrumental in the transformation of granules into secretory vesicles and in their consequent enlargement and (2) that vacuoles are formed by the fusion of large secretory vesicles.

Animals↗
PubMed1999

Secretory organelles in ECL cells of the rat stomach: an immunohistochemical and electron-microscopic study.

ECL cells are numerous in the rat stomach. They produce and store histamine and chromogranin-A (CGA)-derived peptides such as pancreastatin and respond to gastrin with secretion of these products. Numerous electron-lucent vesicles of varying size and a few small, dense-cored granules are found in the cytoplasm. Using confocal and electron microscopy, we examined these organelles and their metamorphosis as they underwent intracellular transport from the Golgi area to the cell periphery. ECL-cell histamine was found to occur in both cytosol and secretory vesicles. Histidine decarboxylase, the histamine-forming enzyme, was in the cytosol, while pancreastatin (and possibly other peptide products) was confined to the dense cores of granules and secretory vesicles. Dense-cored granules and small, clear microvesicles were more numerous in the Golgi area than in the docking zone, i.e. close to the plasma membrane. Secretory vesicles were numerous in both Golgi area and docking zone, where they were sometimes seen to be attached to the plasma membrane. Upon acute gastrin stimulation, histamine was mobilized and the compartment size (volume density) of secretory vesicles in the docking zone was decreased, while the compartment size of microvesicles was increased. Based on these findings, we propose the following life cycle of secretory organelles in ECL cells: small, electron-lucent microvesicles (pro-granules) bud off the trans Golgi network, carrying proteins and secretory peptide precursors (such as CGA and an anticipated prohormone). They are transformed into dense-cored granules (approximate profile diameter 100 nm) while still in the trans Golgi area. Pro-granules and granules accumulate histamine, which leads to their metamorphosis into dense-cored secretory vesicles. In the Golgi area the secretory vesicles have an approximate profile diameter of 150 nm. By the time they reach their destination in the docking zone, their profile diameter is between 200 and 500 nm. Exocytosis is coupled with endocytosis (membrane retrieval), and microvesicles in the docking zone are likely to represent membrane retrieval vesicles (endocytotic vesicles).

Animals↗
PubMed1999

Rat stomach ECL cells up-date of biology and physiology.

The ECL cell is the predominant endocrine cell type in the oxyntic mucosa, displaying typical ultrastructure with numerous cytoplasmic vesicles and electron-dense granules. ECL cells have many features in common with neurons and other peptide hormone-producing endocrine cells, including the ability to produce, store, and secrete chromogranin-A and chromogranin A-derived peptides. In addition, they produce and store histamine and respond with activation and growth to a gastrin challenge. ECL cells are stimulated to secrete histamine as well as other products by gastrin and PACAP and are inhibited by somatostatin, galanin, and prostaglandins. The cytoplasmic vesicles are thought to contain histamine and other secretory products. Mature secretory vesicles occur in the docking zone of the ECL cells, where they constitute the releasable pool of secretory products. Gastrin stimulation will induce exocytosis and degranulation. Histamine released from ECL cells plays a key role in the regulation of parietal cell activity (the gastrin-ECL cell-parietal cell axis). In response to long-term gastrin stimulation, vacuoles and lipofuscin bodies develop in the ECL cells, forming part of a crinophagic pathway by which the ECL cell strives to eliminate superfluous secretory products.

Animals↗
PubMed1999

Pharmacological analysis of CCK2 receptor antagonists using isolated rat stomach ECL cells.

1. Gastrin stimulates rat stomach ECL cells to secrete histamine and pacreastatin, a chromogranin A (CGA)-derived peptide. The present report describes the effect of nine cholecystokinin2 (CCK2) receptor antagonists and one CCK1 receptor antagonist on the gastrin-evoked secretion of pancreastatin from isolated ECL cells. 2. The CCK2 receptor antagonists comprised three benzodiazepine derivatives L-740,093, YM022 and YF476, one ureidoacetamide compound RP73870, one benzimidazole compound JB 93182, one ureidoindoline compound AG041R and three tryptophan dipeptoids PD 134308 (CI988), PD135158 and PD 136450. The CCK1 receptor antagonist was devazepide. 3. A preparation of well-functioning ECL cells (approximately 80% purity) was prepared from rat oxyntic mucosa using counter-flow elutriation. The cells were cultured for 48 h in the presence of 0.1 nM gastrin; they were then washed and incubated with antagonist alone or with various concentrations of antagonist plus 10 nM gastrin (a maximally effective concentration) for 30 min. Gastrin dose-response curves were constructed in the absence or presence of increasing concentrations of antagonist. The amount of pancreastatin secreted was determined by radioimmunoassay. 4. The gastrin-evoked secretion of pancreastatin was inhibited in a dose-dependent manner. YM022, AG041R and YF476 had IC50 values of 0.5, 2.2 and 2.7 nM respectively. L-740,093, JB93182 and RP73870 had IC50 values of 7.8, 9.3 and 9.8 nM, while PD135158, PD136450 and PD134308 had IC50 values of 76, 135 and 145 nM. The CCK1 receptor antagonist devazepide was a poor CCK2 receptor antagonist with an IC50 of about 800 nM. 5. YM022, YF476 and AG041R were chosen for further analysis. YM022 and YF476 shifted the gastrin dose-response curve to the right in a manner suggesting competitive antagonism, while the effects of AG041R could not be explained by simple competitive antagonism. pK(B) values were 11.3 for YM022, 10.8 for YF476 and the apparent pK(B) for AG041R was 10.4.

Animals↗
PubMed1999

Reversibility of cholecystokinin-B/gastrin receptor blockade: a study of the gastrin-ECL cell axis in the rat.

Gastrin acts via cholecystokinin-B/gastrin receptors to control histamine- and chromogranin A-producing ECL cells, which constitute the quantitatively predominant endocrine cell population in the acid-producing part of the rat stomach. Cholecystokinin-B receptor blockade is known to suppress the activity of ECL cells and to prevent their ability to respond to gastrin stimulation. The present study examines the reversibility of long-standing cholecystokinin-B receptor blockade of ECL cells. YM022, a potent and selective cholecystokinin-B receptor antagonist, was administered in a maximally effective dose by continuous subcutaneous infusion for 4 weeks (via osmotic minipumps). The resulting receptor blockade was manifested in elevated serum gastrin concentration (due to the ensuing acid inhibition), while the serum pancreastatin concentration, oxyntic mucosal histidine decarboxylase activity, histidine decarboxylase- and chromogranin A- mRNA levels and histamine and pancreastatin concentrations were lowered. After withdrawal of YM022, all these parameters returned to normal after varying lengths of time. The serum gastrin concentration and the oxyntic mucosal histidine decarboxylase activity returned to normal within a week after termination of treatment. The serum pancreastatin concentration and the mucosal histidine decarboxylase- and chromogranin A-mRNA levels returned to normal within 2 weeks of drug withdrawal. The mucosal pancreastatin and histamine concentrations remained unchanged for about a week before gradually returning to control levels within the next two weeks. Hence, the various effects of cholecystokinin-B receptor blockade of the ECL cells are fully reversible within 1-3 weeks of drug withdrawal.

Animals↗
PubMed1998

Novel aspects of gastrin-induced activation of histidine decarboxylase in rat stomach ECL cells.

The ECL cells in the rat stomach respond to gastrin with secretion of histamine and activation of the histamine-forming enzyme histidine decarboxylase (HDC). In the present study, we have investigated factors that influence gastrin-induced activation of HDC. Gastrin-17 was given by continuous intravenous infusion to fasted and freely fed rats in various doses and for various periods of time. We found that: (1) ECL cells in fasted rats displayed one order of magnitude higher sensitivity to gastrin (3 h infusion) than did ECL cells in fed rats (ED50 0.4 versus 4.0 nmol kg(-1) h(-1)), while the maximum response to gastrin was two times greater in fed rats than in fasted rats; (2) HDC in both fasted and fed rats responded to a high gastrin dose (5 nmol kg(-1) h(-1)) in a biphasic manner with peak activity after 8 h in fasted rats and after 16 h in fed rats. In both groups, the activation was followed by a marked decline in the enzyme activity to almost prestimulation levels 24 h after start of the infusion. A low gastrin dose (0.4 nmol kg(-1) h(-1)) did not induce such a biphasic response. Maximum activation of HDC in fed rats occurred 6 days after starting the infusion of the low gastrin dose and was two times higher than the maximum activation observed after the high gastrin dose; (3) In fasted rats the HDC mRNA level rose in response to the high gastrin dose, peaked after 8 h (twofold increase) and then returned to the prestimulation level. In fed rats the increase was slower, reaching a plateau after 24 h that lasted for 6 days (twofold increase); (4) The translation inhibitor cycloheximide blocked the activation of HDC induced by gastrin (4 h infusion of 5 nmol kg(-1) h(-1)), while the transcription inhibitor actinomycin D, which suppressed the increase in HDC mRNA expression, did not.

Animals↗
PubMed1998

Evidence that peroral calcium does not activate the gastrin-ECL-cell axis in the rat.

The ECL cells are histamine- and pancreastatin-secreting endocrine cells in the oxyntic mucosa, thought to release a blood Ca2+-lowering peptide hormone upon stimulation by gastrin. Previously, we have shown that the ECL cells do not respond to perturbations in blood Ca2+. In the present study, we examine if Ca2+ in the gastric lumen will affect the activity of the gastrin-ECL-cell axis. Freely fed or food deprived (48 h) rats were given an oral load of CaCl2 (or NaCl), and the blood Ca2+ concentration was monitored. The serum gastrin concentration at sacrifice, 3 h after ingestion of CaCl2, was measured together with two parameters of ECL cell activity: the oxyntic mucosal histidine decarboxylase (HDC) activity and the serum pancreastatin concentration. The circulating concentrations of calcitonin and parathyroid hormone (PTH) were also measured. Oral CaCl2 raised the blood Ca2+ in a dose-dependent manner. The two highest doses (which caused damage to the oxyntic mucosa) raised the serum gastrin concentration and the HDC activity in both fed and fasted rats; the serum pancreastatin concentration remained unaffected. Oral CaCl2 raised the serum calcitonin concentration and lowered the serum PTH concentration. The effects of high doses of oral CaCl2 on the serum gastrin concentration and on the oxyntic mucosal HDC activity could be reproduced by a high dose of NaCl. Thus the effects are probably not due to Ca2+ per se. We conclude that the gastrin-ECL-cell axis in the rat does not respond to peroral Ca2+. Since the ECL cells do not respond to either circulating or peroral Ca2+ they are unlikely to secrete a calciotropic hormone.

Administration, Oral↗
PubMed1998

Gastrin stimulates epithelial cell proliferation in the oesophagus of rats.

Gastrin can induce mitotic stimulation in the oxyntic mucosa of the stomach, sometimes leading to abnormal growth. We examined whether gastrin was able to influence cell proliferation in the oesophageal epithelium. Rats were treated with gastrin, omeprazole or saline for 3 days, or were subjected to fundectomy or sham operation. Bromodeoxyuridine labelling (LI) and mitotic (MI) indices were counted in the proliferative zone of the squamous epithelium. Infusion of exogenous gastrin, treatment with omeprazole or fundectomy raised the LI and the MI values in the oesophageal epithelium, indicating that gastrin stimulates cell proliferation in the oesophageal mucosa in the rat.

Animals↗
PubMed1998

Prostaglandins inhibit secretion of histamine and pancreastatin from isolated rat stomach ECL cells.

1. The present study examines the effect of naturally occurring prostanoids and prostaglandin (PG) congeners on gastrin- and pituitary adenylate cyclase-activating peptide (PACAP)-evoked histamine and pancreastatin secretion from isolated rat stomach ECL cells. 2. ECL cells (75-85% purity) were isolated from rat stomach using pronase digestion followed by repeated counter-flow elutriation and cultured for 48 h before secretion experiments. The release of histamine and pancreastatin was determined by radioimmunoassay. 3. None of the PGs tested stimulated the release of either histamine or pancreastatin. 4. PGE1 and PGE2 inhibited both gastrin- and PACAP-evoked histamine and pancreastatin secretion (IC50 = 1-2 x 10(-10) M). Most other naturally occuring prostanoids and PG congeners had no or little inhibitory effect. The PGE analogues misoprostol and sulprostone were more potent (IC50 = 0.9 x 10(-11) M and 2 x 10(-11) M respectively) than PGE1 and PGE2. The rank order of potency was misoprostol > sulprostone > PGE1 = PGE2, suggesting the involvement of the so-called EP3 receptor. 5. The effects of PGs on the stomach ECL cells may be direct or indirect, for instance through the stimulated release of somatostatin from contaminating D cells (2-3%). However, the amount of somatostatin in the cell culture after 48 h was below the limit of detection, and somatostatin immunoneutralization did not prevent misoprostol from inhibiting secretion from the ECL cells. 6. The misoprostol-induced inhibition was reversed by pertussis toxin suggesting the involvement of G-protein subunits G alpha(0) and/or G alpha(i). 7. In view of the potency by which PGE1, PGE2, misoprostol and sulprostone inhibited the stimulated release of histamine and pancreastatin, we suggest that the ECL cells represent a primary target for prostaglandins acting via an EP3 receptor in the oxyntic mucosa. 8. The results suggest that the clinically useful effect of misoprostol as an anti-ulcer drug reflects its ability to inhibit stomach ECL-cell histamine secretion.

Animals↗
PubMed1998

Endogenous hypergastrinaemia does not promote growth of colonic mucosa or of a transplanted colon adenocarcinoma in rats.

BACKGROUND/OBJECTIVE: Gastrin is trophic for the mucosa of the acid-producing part of the rat stomach, notably the histamine-producing ECL cells. Gastrin is said to stimulate growth also of colonic mucosa and colon cancer. The purpose of the present study was to examine whether endogenous hypergastrinaemia had trophic effects on normal colonic mucosa and transplanted colon adenocarcinoma in rats. METHODS: Rats were subjected to fundectomy (surgical removal of the acid-producing part of the stomach) or treatments known to induce endogenous hypergastrinaemia. The treatments included refeeding after 48 h of food deprivation or administration of omeprazole (400 micromol/kg/day, orally). Other operations included colostomy and sham operation. A K12-cell line, originally established from a 1,2-dimethylhydrazine-induced colon adenocarcinoma, was used for transplantation. The rates of cell proliferation were determined in the oxyntic and colonic mucosa and in the tumour by measuring the proportion of the cells that accumulated bromodeoxyuridine in their nuclei, i.e. the labelling index (LI). The thickness of the oxyntic mucosa and the activity of histidine decarboxylase (HDC), the histamine-forming enzyme of the ECL cells, were measured. In addition, the thickness of the colonic mucosa and the weight and volume of the tumour were measured. RESULTS: Refeeding or treatment with a single dose of omeprazole in fasted rats raised the serum gastrin concentration and the LI and HDC activity in the oxyntic mucosa; refeeding but not omeprazole raised the LI in the colonic mucosa. In fed rats, hypergastrinaemia induced by fundectomy or treatment with omeprazole (for 10 days) failed to affect either the LI or the thickness of the mucosa of the proximal colon and the excluded distal colon of the colostomized rats. Fundectomy failed to stimulate the growth of the tumour transplants. CONCLUSION: Endogenous hypergastrinaemia did not induce trophic effects on rat colonic mucosa and did not promote growth of a transplanted colon adenocarcinoma in the rat.

Adenocarcinoma↗
PubMed1998

Sustained cholecystokinin-B/gastrin receptor blockade does not impair basal or histamine-stimulated acid secretion in chronic gastric fistula rats.

Gastrin is a physiologically important secretagogue. It is thought to stimulate parietal cells indirectly by mobilizing histamine from enterochromaffin-like (ECL) cells in the oxyntic mucosa. Gastrin stimulates the secretory activity and growth of the ECL cells via an action on cholecystokinin-B/gastrin receptors. Acute cholecystokinin-B/gastrin receptor blockade is known to inhibit gastrin-stimulated acid secretion but whether sustained cholecystokinin-B/gastrin receptor blockade will impair basal, gastrin- and histamine-stimulated acid secretion remains uncertain. The present study was designed to study the effect of long-term (4 weeks) cholecystokinin-B/gastrin receptor blockade on basal and stimulated acid secretion in conscious rats. The selective cholecystokinin-B/gastrin receptor antagonist YM022 (3 mumol.kg-1.hr-1) was given to gastric fistula rats by continuous subcutaneous infusion via osmotic minipumps for various times from 2 hr to 4 weeks. Basal, gastrin- and histamine-stimulated acid secretion were examined during and after cessation of treatment. Basal and histamine-stimulated acid secretion was not affected by YM022 during the 4 week period of administration, whereas gastrin-induced acid secretion was inhibited. YM022 induced hypergastrinaemia in freely fed rats but did not affect the serum gastrin level in fasted rats. The serum gastrin concentration and gastrin-induced acid secretion returned to control levels 3-7 days after termination of YM022 administration.

Animals↗
PubMed1997

Functional impairment of the individual rat stomach ECL cell in response to sustained hypergastrinemia.

ECL cells in the oxyntic mucosa secrete histamine and pancreastatin in response to gastrin. The present study examined gastrin-evoked ECL-cell responses over a 10-week time span in terms of individual ECL cells and unit ECL cell volume. Rats were treated with omeprazole (400 micromol/kg per day orally). The concentrations of gastrin and pancreastatin in serum and of histamine and pancreastatin in the oxyntic mucosa were measured as was the activity of the oxyntic mucosal histidine decarboxylase (HDC). The ECL cells were visualized by immunostaining of histamine and examined by electron microscopy. The total ECL cell number and volume, and the mean ECL cell diameter and volume were determined. The HDC, chromogranin A (CGA) and cholecystokinin-B (CCK-B) receptor mRNA concentrations were determined. In terms of individual ECL cells and unit ECL cell volume, the serum pancreastatin concentration, the oxyntic mucosal histamine content, HDC activity, and HDC, CGA and CCK-B receptor mRNA contents increased slowly at first and then leveled off or started to decline after 2 weeks. After 10 weeks all ECL-cell parameters (expressed per unit ECL cell volume) were back to or approaching the starting value. In conclusion, sustained hypergastrinemia first activates each individual ECL cell (with a peak after 1-2 weeks) and then causes gradual functional impairment, the activity returning towards the pre-stimulation level.

Animals↗
PubMed1997

Neurohormonal regulation of histamine and pancreastatin secretion from isolated rat stomach ECL cells.

ECL cells are numerous in the acid-producing part of the rat stomach. They are rich in histamine and pancreastatin, a chromogranin A-derived peptide, and they secrete these products in response to gastrin. We have examined how isolated ECL cells respond to a variety of neuromessengers and peptide hormones. Highly purified (85%) ECL cells were collected from rat stomach using repeated counter-flow elutriation and cultured for 48 h before experiments were conducted. The ECL cells responded to gastrin, sulphated cholecystokinin-8 and to high K+ and Ca2+ with the parallel secretion of histamine and pancreastatin. Glycine-extended gastrin was without effect. Forskolin, an activator of adenylate cyclase, induced secretion, whereas isobutylmethylxanthine, a phosphodiesterase inhibitor, raised the basal release without enhancing the gastrin-evoked stimulation. Maximum stimulation with gastrin resulted in the release of 30% of the secretory products. Numerous neuromessengers and peptide hormones were screened for their ability to stimulate secretion and to inhibit gastrin-stimulated secretion. Pituitary adenylate cyclase activating peptide (PACAP)-27 and -38 stimulated secretion of both histamine and pancreastatin with a potency greater than that of gastrin and with the same efficacy. Related peptides, such as vasoactive intestinal peptide, helodermin and helospectin, stimulated secretion with lower potency. The combination of EC100 gastrin and EC50 PACAP produced a greater response than gastrin alone. None of the other neuropeptides or peptide hormones tested stimulated secretion. Serotonin, adrenaline, noradrenaline and isoprenaline induced moderate secretion at high concentrations. Muscarinic receptor agonists did not stimulate secretion, and histamine and selective histamine receptor agonists and antagonists were without effect. This was the case also with GABA, aspartate and glutamate. Somatostatin and galanin, but none of the other agents tested, inhibited gastrin-stimulated secretion. Our results reveal that not only gastrin but also PACAP is a powerful excitant of the ECL cells, that not only somatostatin, but also galanin can suppress secretion, that muscarinic receptor agonists fail to evoke secretion, and that histamine (and pancreastatin) does not evoke autofeedback inhibition.

Animals↗
PubMed1997

Expression of the chromogranin A-derived peptides pancreastatin and WE14 in rat stomach ECL cells.

The ECL cells constitute the predominant endocrine cell population in the mucosa of the acid-secreting part of the stomach (fundus). They are rich in chromogranin A (CGA), histamine and histidine decarboxylase (HDC). They secrete CGA-derived peptides and histamine in response to gastrin. The objective of this investigation was to examine the expression of pancreastatin (rat CGA266-314) and WE14 (rat CGA343-356) in rat stomach ECL cells. The distribution and cellular localisation of pancreastatin- and WE14-like immunoreactivities (LI) were analysed by radioimmunoassay and immunohistochemistry with antibodies against pancreastatin, WE14 and HDC. The effect of food deprivation on circulating pancreastatin-LI was examined in intact rats and after gastrectomy or fundectomy. Rats received gastrin-17 (5 nmol/kg/h) by continuous intravenous infusion or omeprazole (400 micromol/kg) once daily by the oral route, to induce hypergastrinemia. CGA-derived peptides in the ECL cells were characterised by gel permeation chromatography. The expression of CGA mRNA was examined by Northern blot analysis. Among all of the endocrine cells in the body, the ECL cell population was the richest in pancreastatin-LI, containing 20-25% of the total body content. Food deprivation and/or surgical removal of the ECL cells lowered the level of pancreastatin-LI in serum by about 80%. Activation of the ECL cells by gastrin infusion or omeprazole treatment raised the serum level of pancreastatin-LI, lowered the concentrations of pancreastatin- and WE14-LI in the ECL cells and increased the CGA mRNA concentration. Chromatographic analysis of the various CGA immunoreactive components in the ECL cells of normal and hypergastrinemic rats suggested that these cells respond to gastrin with a preferential release of the low-molecular-mass forms.

Animals↗
PubMed1997

Electroconvulsive treatment evokes release of preprotachykinin-A mRNA into the cerebrospinal fluid and ocular aqueous humor of rabbits.

Following electroconvulsive treatment (ECT) of rabbits, preprotachykinin-A (PPT-A) mRNA was detected by Southern blot analysis of polymerase chain reaction (PCR)-amplified products in the cerebrospinal fluid (CSF) and aqueous humor of the eye. In contrast, no PPT-A mRNA could be detected in samples from untreated animals. In addition, several neuropeptides (substance P, neuropeptide Y, cholecystokinin, calcitonin gene-related peptide and pituitary adenylate cyclase activating peptide) were released into the CSF (and aqueous humor) following ECT. The results suggest that PPT-A mRNA was released together with neuropeptides into the CSF and aqueous humor in response to ECT. Indeed, previous studies have suggested that neurons can release neuropeptide mRNAs and that neurons are capable of taking up and expressing foreign mRNA. If neuropeptide mRNA can be taken up and utilized by another neuronal population, it might explain instances when neurons display 'phenotypic switch', i.e. the transient expression of novel neuropeptides.

Animals↗
PubMed1997

Capsaicin-evoked release of pituitary adenylate cyclase activating peptide (PACAP) and calcitonin gene-related peptide (CGRP) from rat spinal cord in vivo.

Capsaicin-evoked release of pituitary adenylate cyclase activating peptide (PACAP)-like immunoreactivity (LI) from rat spinal cord was examined in vivo. In anaesthetized rats, a catheter was inserted through the atlanto-occipital membrane into the subarachnoid space at the level of the sacral spinal cord for infusion of artificial cerebrospinal fluid. Another catheter was placed in the cisternal opening for outflow. Blood pressure was monitored and kept stable during the experiment. Perfusion samples were analyzed for PACAP and calcitonin gene-related peptide (CGRP) by radioimmunoassay. The addition of capsaicin (10 microM) to the perfusate elevated the concentrations of PACAP-27-LI in the artificial cerebrospinal fluid by 177%, PACAP-38-LI by 93% and CGRP-LI by 692%. In view of the presence of PACAP-immunoreactive nerve fibres in the superficial layers of the dorsal horn and the expression of PACAP in the small sized neurons in the dorsal root ganglia, the findings suggest that PACAP is released into the artificial cerebrospinal fluid from C-fibres in the spinal cord. PACAP conceivably plays a modulating role in nociception.

Animals↗