PubMed Health⌕ Search

Biomedical subjects

R Håkanson

Publications and source records attributed to R Håkanson.

At least 73 records · Page 4Linked to original sources
PubMed1997

Evidence that rat stomach ECL cells represent the main source of circulating pancreastatin.

Recently, we showed that the ECL cells in the oxyntic mucosa of the rat stomach are an important source of circulating pancreastatin, a fragment of chromogranin A. The present study examined how much the ECL cells contribute to the circulating levels of pancreastatin during omeprazole-evoked hypergastrinemia. Rats received omeprazole (400 mumol kg-1 day-1) by the oral route for 3 weeks. Two weeks after the start of the treatment, the rats were subjected to a sham operation or fundectomy. The concentrations of gastrin and pancreastatin in serum were monitored before and after the operations. The ECL cells were visualized by pancreastatin immunostaining and their number was determined. The activity of oxyntic mucosal histidine decarboxylase (HDC) was measured before and after 2 weeks of omeprazole treatment. Omeprazole-induced hypergastrinemia resulted in elevated serum pancreastatin and increased oxyntic mucosal HDC activity. Pancreastatin-immunoreactive cells were equally numerous before and after 2 weeks of omeprazole treatment. After surgical removal of the ECL cells by fundectomy, the serum gastrin concentration remained high whereas the serum pancreastatin concentration decreased by 90%. We conclude that the ECL cells in omeprazole-treated rats are responsible for 90% of circulating pancreastatin.

Animals↗
PubMed1997

Effects of fasting on the expression of gastrin, cholecystokinin, and somatostatin genes and of various housekeeping genes in the pancreas and upper digestive tract of rats.

It is generally accepted that while the gene expression of many gut hormones in the pancreas and upper digestive tract is influenced by the prandial state, the expression of house-keeping genes (used as internal standards) is stable. We have analysed how food deprivation affects the messenger (m) RNA expression of gastrin, cholecystokinin (CCK), and somatostatin and of house-keeping genes glyceraldehyde-3-phosphate dehydrogenase (GAPDH), beta-actin and 18S ribosomal (r) RNA. RNA, isolated from oxyntic, antral and duodenal mucosa and pancreas, was subjected to Northern blot analysis using complementary RNA probes. Compared to fed rats, food-deprived rats exhibited reduced mRNA expression of gastrin (antrum), somatostatin (antrum), CCK (duodenum), GAPDH (all tissues studied) and beta-actin (all tissues studied) and unchanged 18S rRNA expression. We conclude that the assessment of gut hormone mRNA expression may be greatly influenced by the choice of internal standard and that 18S rRNA is superior.

Actins↗
PubMed1997

Ocular inflammation induced by electroconvulsive treatment: contribution of nitric oxide and neuropeptides mobilized from C-fibres.

1. Electroconvulsive treatment (ECT) of rabbits produced ocular inflammation consisting of conjunctival hyperaemia, miosis and protein extravasation into the aqueous humour, reflected by the so-called aqueous flare response (AFR): the maximal reduction in pupil size was 3.8 +/- 0.1 mm (s.e. of mean, n = 16) while the maximal AFR was 28.1 +/- 2.8 (arbitrary units). 2. ECT also caused release of substance P (SP), pituitary adenylate cyclase-activating peptide (PACAP)-27, -38 and calcitonin gene-related peptide (CGRP). The concentrations of SP and CGRP in the aqueous humour of normal, untreated eyes were 10.6 +/- 1.4 and 117.4 +/- 12.4 pmol l-1, respectively, while the concentrations of PACAP-27 and -38 were below the detection limit. After ECT the concentrations of SP, PACAP-27, -38 and CGRP were 65.0 +/- 9.6, 46.9 +/- 8.4, 50.2 +/- 5.4 and 1109.9 +/- 133.1 pmol l-1, respectively (s.e. of mean, n = 12). Conceivably, ECT evoked an antidromic activation of sensory neurones in the trigeminal ganglion with the consequent release of neuropeptides from C-fibres in the uvea and the development of neurogenic inflammation. 3. Rabbits received the nitric oxide (NO) synthase inhibitor, NG-nitro-L-arginine methyl ester (L-NAME, 200 mg kg 1, i.v.). This pretreatment inhibited the ECT-evoked conjunctival hyperaemia, miosis and AFR: under these circumstances the maximal reduction in pupil size was 1.9 +/- 0.1 mm while the maximal AFR was 2.7 +/- 0.9 (n = 16). L-NAME also inhibited the ECT-evoked release of SP, PACAP-27, -38 and CGRP into the aqueous humour; the concentrations of SP and CGRP were 13.2 +/- 1.5 and 204.8 +/- 33.5 pmol l-1, respectively, while PACAP-27 and -38 were below the detection limit (n = 12). 4. The ECT-evoked miosis was also inhibited by pretreatment with the tachykinin receptor antagonist D-Pal9 spantide 11 (90 nmol, intravitreal injection); under these circumstances the maximal reduction in pupil size was only 0.7 +/- 0.03 mm, indicating an important role for SP in the miotic response. Pretreatment of the eye with capsaicin, which is known to cause functional ablation of C-fibres, inhibited the conjunctival hyperaemia, miosis and AFR by 40-50%; the maximal reduction in pupil size being 2.2 +/- 0.2 mm and the maximal AFR 13.8 +/- 2.1 (arbitrary units) (n = 8). 5. The results suggest (1) that ECT evokes ocular inflammation through antidromic C-fibre activation; (2) that SP contributes to the ECT-evoked miosis; and (3) that NO contributes to the antidromic C-fibre activation and possibly to the vascular responses mediated by the C-fibre transmitters.

Animals↗
PubMed1997

Time-course of deactivation of rat stomach ECL cells following cholecystokinin B/gastrin receptor blockade.

1 The so-called enterochromaffin-like (ECL) cells constitute 65-75% of the endocrine cells in the acid-producing part of the rat stomach. They produce and secrete histamine and pancreastatin, a chromogranin A (CGA)-derived peptide, in response to gastrin, Cholecystokinin (CCK)B/gastrin receptor blockade is known to suppress their activity. 2 We have examined the time course of the deactivation of the ECL cells following treatment with the selective CCKB receptor antagonists RP73870 and YM022. The drugs were given by continuous subcutaneous infusion for a time span of 1 h to 3 weeks and the serum gastrin concentration and various ECL cell parameters were measured (oxyntic mucosal histidine decarboxylase (HDC) activity, histamine and pancreastatin concentrations, HDC mRNA and CGA mRNA levels, and circulating pancreastatin concentration). 3 The two antagonists caused a prompt and dramatic decline in the oxyntic mucosal HDC activity and HDC mRNA level. The HDC activity started to decline after 1-2 h, was reduced by 60-70% after 6 h and was maximally suppressed (80-90%) after 24-48 h. The HDC mRNA level was reduced after 12 h and was at about 20% of the pretreatment level after 2-4 days of infusion. The ECL cell histamine concentration was lowered by about 50% after 7-10 days. 4 RP73870 and YM022 lowered the serum pancreastatin concentration and the oxyntic mucosal CGA mRNA level. The serum pancreastatin concentration was reduced by 40% after 6 h and the reduction was maximal after 2-3 days. A decline in the oxyntic mucosal CGA mRNA level was noted after 12 h with a maximal reduction after 2-4 days of infusion. The ECL cell pancreastatin concentration was reduced by 30-40% after 3 weeks. 5 The infusion of RP73870 and YM022 induced hypergastrinaemia. The serum gastrin concentration started to rise after 2-4 h, there was a 2 fold increase after 6 h and maximal increase (3-4 fold) after 2-3 days of treatment. 6 In conclusion, CCKB/gastrin receptor blockade promptly deactivates the ECL cells. Deactivation, manifested in a greatly reduced HDC activity, was apparent after 1-2 h of the infusion. The serum pancreastatin concentration and the oxyntic mucosal HDC mRNA and CGA mRNA levels were greatly reduced after 1-2 days. The ECL cell concentrations of histamine and pancreastatin declined quite slowly by comparison.

Animals↗
PubMed1997

Pituitary adenylate cyclase activating peptide (PACAP) in salivary glands of the rat: origin, and secretory and vascular effects.

Pituitary adenylate cyclase activating peptide (PACAP)-38, injected i.v. to the anaesthetized rat, evoked secretion of saliva from the three major salivary glands, the submandibular glands responding with the greatest and the sublingual glands with the smallest volumes. The parotid saliva was rich in amylase and protein. In vitro, pieces of parotid and submandibular gland tissues released K+ and protein in response to PACAP-38, with atropine and adrenoceptor antagonists present. The blood flow in the submandibular gland increased in response to PACAP-38, despite a marked fall in mean aortic blood pressure. PACAP is a vasoactive intestinal peptide (VIP)-like neuropeptide. A comparison between the two peptides showed PACAP-38 to be more effective than VIP with respect to vascular responses and less or equi-effective with VIP with respect to the secretory responses, thus suggesting the involvement of PACAP type I and type II receptors, respectively PACAP-38 and -27 were present in the parotid gland as judged by radioimmunoassay, the concentration of the former being about twice that of the latter. Parasympathetic denervation, by cutting the auriculo-temporal nerve, reduced the total parotid gland contents of PACAP-38 and -27 by 23 and 44%, respectively (compared with a previously demonstrated 95% reduction of VIP). Sympathetic denervation, section of the facial nerve or treatment with the sensory neurotoxin capsaicin did not affect the content of PACAP. The difference in efficacy between PACAP and VIP in the vascular and secretory responses as well as the difference in localization suggest that the two peptides play different physiological roles in the salivary glands.

Animals↗
PubMed1997

Cholecystokinin-B/gastrin receptor blockade suppresses the activity of rat stomach ECL cells.

Gastrin controls the histamine- and chromogranin A-producing enterochromaffin-like (ECL) cells, the predominant endocrine cell population in the acid-producing part of the rat stomach. They are responsible for most of the circulating pancreastatin, a chromogranin A-derived peptide. The present study examines the ability of two potent and highly selective cholecystokinin-B/gastrin receptor antagonists, RP73870 and YM022, to incapacitate the ECL cells. The two antagonists were given by continuous subcutaneous infusion to otherwise untreated rats and to hypergastrinaemic rats treated with gastrin-17 (continuous subcutaneous infusion) or omeprazole (orally) for 7 days. Several parameters reflecting ECL cell activity were measured: The oxyntic mucosal histidine decarboxylase activity, the histamine concentration, the histidine decarboxylase mRNA and chromogranin A mRNA concentrations, and the serum pancreastatin concentration. In addition, the serum gastrin concentration was measured. RP73870 and YM022 greatly lowered the oxyntic mucosal histidine decarboxylase activity and the histidine decarboxylase mRNA and chromogranin A mRNA concentrations, and also reduced the oxyntic mucosal histamine concentration and the serum pancreastatin concentration. Moreover, they raised the serum gastrin concentration. With respect to blockade of histidine decarboxylase activity, 1.0 mumol.kg-1.hr-1 was an almost maximally effective dose for both RP73870 and YM022. The corresponding ID50 values were 0.04 and 0.05 mumol.kg-1.hr-1. RP73870 and YM022 inhibited the hypergastrinaemia-evoked rise in all ECL-cell parameters. The results suggest that sustained cholecystokinin-B/gastrin receptor blockade causes lasting deactivation of the ECL cells.

Animals↗
PubMed1997

Evaluation of three novel cholecystokinin-B/gastrin receptor antagonists: a study of their effects on rat stomach enterochromaffin-like cell activity.

Gastrin stimulates rat stomach enterochromaffin-like (ECL) cells via activation of cholecystokinin-B/gastrin receptors. The stimulation is manifested in the activation of the histamine-forming enzyme histidine decarboxylase and in the secretion of histamine and pancreastatin, a chromogranin A-derived peptide. We have examined the short-term effects of three novel cholecystokinin-B/gastrin receptor antagonists (YF476, JB93182 and AG041R) on the ECL cells in intact fasted rats. The drugs and/or gastrin were infused intravenously for 3 hr and the oxyntic mucosal histidine decarboxylase activity and the serum pancreastatin concentration were measured. We also studied the effects of the three drugs on gastric emptying in mice, a cholecystokinin-A receptor-mediated response. YF476, JB93182 and AG041R antagonized the gastrin-evoked histidine decarboxylase activation in a dose-dependent manner. YF476, JB93182 and AG041R induced maximal inhibition at 0.03, 0.1 and 0.1 mumol kg-1 hr-1, respectively; the corresponding ID50 values were 0.002, 0.008, and 0.01 mumol kg-1 hr-1. YF476 was selected for further analysis. It produced a rightward shift of the gastrin dose-response curve, consistent with competitive inhibition. Moreover, it antagonized the omeprazole-evoked histidine decarboxylase activation and the gastrin- and omeprazole-induced rise in the circulating pancreastatin concentration. None of the three drugs tested inhibited gastric emptying or prevented the cholecystokinin-8s-induced inhibition of gastric emptying at the doses tested. The results show that YF476, JB93182 and AG041R are potent and selective cholecystokinin-B/ gastrin receptor antagonists, and that YF476 is 4-5 times more potent than JB93182 and AG041R.

Animals↗
PubMed1997

The trophic response of rat pancreas to sulfated cholecystokinin-8 is dose- and time-dependent and not affected by vagotomy or atropine.

Cholecystokinin (CCK) stimulates pancreatic enzyme secretion and growth. This study establishes the dose/plasma concentration--and time--response relationships for the trophic effect of CCK on the rat pancreas and evaluates the importance of vagal innervation and muscarinic receptors for the trophic effect. Rats received sulfated CCK-8 (CCK-8s) by continuous subcutaneous infusion. Different doses and different times of treatment were tested. The trophic effect was determined as wet weight and DNA content of the pancreas. The pancreatic weight and DNA content were found to depend not only on the plasma concentration of CCK-8s but also on the duration of treatment. The EC50 value was 40 pmoles CCK-8s per liter. This value should be compared with plasma CCK-8s concentrations of 2-4 pmol/l in intact fed rats. Maximum trophic effect was observed after 7-14 days of infusion. We conclude that although physiologically relevant concentrations of CCK-8s may be important for the maintenance of the pancreas they do not induce growth. In another experiment atropinized, vagally denervated and intact rats were treated with a maximally effective dose of CCK for four days. The trophic effect of CCK-8s was unaffected by vagotomy or atropinization.

Animals↗
PubMed1997

Increased expression of cholecystokinin-A receptor mRNA in pancreas and cholecystokinin-B receptor mRNA in oxyntic mucosa after porta-caval shunting in rats.

Porta-caval shunting enhances the trophic effects of cholecystokinin (CCK)-A receptor activation on the pancreas and of CCK-B receptor activation on the ECL cells in the oxyntic mucosa of the rat. The aim of the present study was to study the expression of CCK-A and CCK-B receptor mRNA after porta-caval shunting. Different doses of sulfated CCK-8 (CCK-8s) were administered to porta-caval shunting rats and sham-operated rats, 4 weeks after the operations. The pancreatic wet weight and DNA content were measured and the ECL cells in the oxyntic mucosa were counted after four days of continuous subcutaneous infusion. Total RNA was isolated from pancreas and oxyntic mucosa for Northern blot analysis of CCK-A and CCK-B receptor mRNA. Porta-caval shunting per se did not affect plasma CCK level nor the weight or DNA content of the pancreas, but resulted in increased number of ECL cells despite the fact that the serum gastrin concentration was reduced. The trophic response of the pancreas to low doses of CCK-8s was greater in porta-caval shunted rats than in sham-operated rats. Porta-caval shunted rats displayed an increased CCK-A receptor mRNA concentration in the pancreas (after stimulation with CCK-8s) and an increased CCK-B receptor mRNA concentration in the oxyntic mucosa. In conclusion, the porta-caval shunting-evoked enhancement of the trophic effect of CCK-A receptor activation on the pancreas and of CCK-B receptor activation on the ECL cells is associated with enhanced expression of CCK-A receptor mRNA in the pancreas and of CCK-B receptor mRNA in the oxyntic mucosa.

Animals↗
PubMed1996

PACAP occurs in sensory nerve fibers and participates in ocular inflammation in the rabbit.

PACAP is a sensory neuropeptide; it occurs together with CGRP in a population of C fibers in the rabbit eye. PACAP is likely to be involved in the inflammatory response in as much as PACAP-induced responses mimic the symptoms of inflammation and because the concentration of PACAP-LI in the aqueous humor increased greatly in response to noxious stimuli. The observation that capsaicin releases both PACAP and CGRP from the iris and ciliary body supports the view that PACAP is present in C fibers in the rabbit eye.

Animals↗
PubMed1996

Gastrin-evoked secretion of pancreastatin and histamine from ECL cells and of acid from parietal cells in isolated, vascularly perfused rat stomach. Effects of isobutyl methylxanthin and alpha-fluoromethylhistidine.

The ECL cells in the rat stomach release pancreastatin and histamine in response to gastrin stimulation. The present study compares the release of pancreastatin and histamine from the ECL cells and the secretion of acid from the parietal cells in response to gastrin, and examines how a markedly reduced histamine content in the ECL cells will affect the gastrin-evoked release of pancreastatin and the secretion of gastrin acid. Totally isolated, vascularly perfused stomachs were prepared from fasted rats. Some of the rats had been pre-treated for 24 h with (alpha-fluoromethylhistidine (alpha-FMH), resulting in 80% depletion of oxyntic mucosal histamine (mainly ECL-cell histamine). The stomachs were perfused with rat gastrin-17, alpha-FMH, isobutyl methylxanthine (IBMX), or vehicle in various combinations for 8 h. The venous outflow was collected (30-min samples) for determination of histamine and pancreastatin-like immunoreactivity (LI) and the gastric luminal outflow was collected for determination of H+. Gastrin raised the outflow of pancreastatin-LI and histamine but did not raise the acid output unless IBMX was added. The outflow of pancreastatin-LI and histamine was greater after gastrin + IBMX (at least during the first 4-h period) than after gastrin alone. alpha-FMH reduced gastrin-evoked histamine outflow but did not affect gastrin-evoked pancreastatin-LI outflow. Also the acid output in response to gastrin + IBMX was much reduced by alpha-FMH. In conclusion, increased levels of intracellular cAMP enhanced the gastrin-evoked release of pancreastatin-LI and histamine from the ECL cells and made it possible for histamine, released from the ECL cells, to cause acid secretion from the parietal cells. ECL-cell histamine depletion reduced the gastrin-evoked acid secretion; it did not affect the gastrin-evoked release of pancreastatin-LI.

1-Methyl-3-isobutylxanthine↗
PubMed1996

Release of preprotachykinin-A mRNA from rabbit iris upon C-fibre stimulation.

It is usually said that axons and nerve terminals do not contain messenger RNA (mRNA) and that peptide transmitters are packaged in granules and transported towards the periphery of the neuron. However, several recent reports challenge this view by showing evidence of the existence of mRNA in axons. In the present study, we demonstrate the existence of mRNA coding for gamma-preprotachykinin-A in rabbit iris by Northern blot analysis and Southern blot analysis of the polymerase chain reaction (PCR)-amplified products. Interestingly, mRNA coding for gamma-preprotachykinin-A was detected also in aqueous humor from eyes exposed to injury (infrared irradiation of the iris or retrobulbar injection of the C-fibre excitant capsaicin), but not from contralateral eyes and normal eyes of untreated rabbits. Our results suggest that the mRNA coding for gamma-preprotachykinin-A occurs in C-fibres in the iris and that it is released into the aqueous humor together with tachykinins in response to C-fibre stimulation.

Animals↗
PubMed1996

Ultrastructure of enterochromaffin-like cells in rat stomach: effects of alpha-fluoromethylhistidine-evoked histamine depletion and hypergastrinemia.

Histamine-producing enterochromaffin-like (ECL) cells are numerous in the oxyntic mucosa of the rat stomach. They respond to gastrin by secretory activation, hypertrophy and hyperplasia. They contain cytoplasmic granules (median profile diameter 120 nm), secretory vesicles (180 nm) and microvesicles (70 nm). alpha-Fluoromethylhistidine (alpha-FMH) depletes histamine from the ECL cells by inhibiting the histamine-forming enzyme histidine decarboxylase. Long-term hypergastrinemia, evoked by omeprazole, increases the ECL-cell histamine concentration. The way in which chronic histamine depletion affects omeprazole-induced ECL-cell hypertrophy, and the ways in which granules and vesicles in the ECL cells respond to alpha-FMH and/or omeprazole have been studied. Rats were treated with alpha-FMH (3 mg/kg per h subcutaneously), omeprazole (400 micromol/kg per day orally), alpha-FMH+omeprazole, or vehicle for 6 weeks. ECL cell profiles in electron micrographs were analysed panimetrically. The results show that the omeprazole-evoked hypertrophy of the ECL cells is not affected by depletion of ECL-cell histamine, thereby supporting the view that ECL-cell histamine is not important for full expression of the gastrin-evoked trophic effects on the ECL cells. The loss of ECL-cell histamine following treatment with alpha-FMH and with alpha-FMH+omeprazole is associated with a greatly reduced size of the secretory vesicle compartment. The granules, on the other hand, are unaffected by alpha-FMH and alpha-FMH+omeprazole. Omeprazole treatment leads to the appearance of numerous vacuoles (with profile diameter greater than 500 nm); such vacuoles are not observed in the ECL cells of rats treated with alpha-FMH or alpha-FMH+omeprazole. The omeprazole-induced increase in ECL-cell histamine is associated with an increase in the compartment composed of secretory vesicles and vacuoles. The findings support the hypothesis that secretory vesicles (and vacuoles) represent a major storage site of ECL-cell histamine.

Animals↗
PubMed1996

Time course of hypertrophic and ultrastructural responses of rat stomach enterochromaffin-like cells to sustained hypergastrinemia.

Previously, we have investigated the effects of short-term (minutes to hours) and long-term (weeks to months) stimulation with gastrin on the histamine-producing enterochromaffin-like (ECL) cells in the oxyntic mucosa of rat stomach. The present study examines the response of the ECL cells of freely fed rats to sustained hypergastrinemia over a time span of a few hours to four weeks. Sustained hypergastrinemia was induced by the continuous subcutaneous infusion of human Leu15-gastrin-17. The histidine decarboxylase (HDC) activity and histamine concentration in the oxyntic mucosa were monitored throughout the study. ECL cell profiles in electron micrographs were analysed planimetrically. The HDC activity displayed a 4-fold increase within the first two days. Subsequently, it remained at a plateau. The histamine concentration increased 2- to 3-fold in response to gastrin. The rise in histamine was slower than the rise in HDC activity. At no time point was there a reduced concentration of histamine. The ECL cells increased in size after 4 days of hypergastrinemia, reaching a maximum cell profile area after 2 weeks and remaining enlarged for the duration of the study. The secretory vesicles were reduced in number after 1 day, returning gradually to the pre-stimulation value thereafter; their volume density remained reduced during the 6-day observation period. Vacuoles started to appear after 1 day of hypergastrinemia and their number and volume density increased, reaching a maximum after 4 days. The number and volume density of the microvesicles increased and plateaued after 2 days of hypergastrinemia. The number of granules per cell profile was unaffected but their volume density was greatly reduced after 4 days of hypergastrinemia (reflecting the ECL cell hypertrophy). The present findings establish the time course of activation of the ECL cells in response to sustained hypergastrinemia over a time span of a few hours to four weeks; a new "steady state" situation at a high level of activity has been established after about a week.

Animals↗
PubMed1996

The contribution of nitric oxide to endotoxin-induced ocular inflammation: interaction with sensory nerve fibres.

1. The actions of nitric oxide (NO) have been investigated in an endotoxin-evoked ocular inflammatory model in the rabbit, with particular emphasis on the relationship between NO, sensory nerves (C-fibres) and the C-fibre neuropeptides, calcitonin gene-related peptide (CGRP) and pituitary adenylate cyclase activating peptide (PACAP). 2. Endotoxin, injected intravitreally, evoked inflammatory responses, i.e. conjunctival hyperaemia, miosis and protein extravasation, reflected by the aqueous flare response (AFR). In control rabbits, the maximum AFR was 66.5 +/- 9.5 (arbitrary units). Pretreatment with the NO synthase (NOS) inhibitor, NG-nitro-L-arginine (L-NAME, 200 mg kg-1) given by intravenous injection, inhibited the endotoxin-evoked responses; the AFR was 16.5 +/- 1.9 (n = 8, P < 0.001) and the conjunctival hyperaemia was abolished. 3. Endotoxin-evoked ocular inflammation is associated with the release of CGRP and PACAP from C-fibres. In the eyes challenged with endotoxin, the concentrations of PACAP-27, -38 and CGRP in the aqueous humour were 58.2 +/- 10.9, 54.4 +/- 12.4 and 5526 +/- 519 (pmoll'), respectively. L-NAME inhibited the release of PACAP-27, -38 and CGRP; the concentrations were 14.3 +/- 2.5, 13.5 +/- 2.5 and 510 +/- 67 (pmoll-1), respectively (n = 8, P < 0.01 or 0.001). 4. Intravitreal injection of 0.3 nmol CGRP induced conjunctival hyperaemia and AFR; the maximum AFR was 140.2 +/- 11.4. L-NAME suppressed the response induced by CGRP; the AFR was 23.4 +/- 5.5 (n = 8, P < 0.001). L-NAME abolished the conjunctival hyperaemia induced by PACAP-27 and -38 (0.3 nmol) and reduced the AFR. 5. The inflammatory cells that infiltrated the uvea, cornea and aqueous humour in large numbers in response to intravitreal injection of endotoxin were found to express inducible NOS. L-NAME prevented the appearance of such cells. 6. Our findings suggest that NO plays an important role in the endotoxin-evoked ocular inflammation in the rabbit: NO activates C-fibres causing release of C-fibre neuropeptides into the aqueous humour. In addition, NO mediates scme of the ocular effects of CGRP and PACAP, since L-NAME suppressed the AFR induced by these peptides.

Animals↗
PubMed1996

Effect of cholecystokinin-B/gastrin receptor blockade on gastric acid secretion in conscious rats.

Gastrin, histamine and acetylcholine are physiological stimuli of gastric acid secretion. The cholecystokinin-B/gastrin receptor antagonists YM022 and RP73870 were used to study the effect of gastrin receptor blockade on acid secretion. Gastrin, histamine, insulin or bethanechol were administered to conscious gastric fistula rats with or without the concomitant intravenous infusion of YM022 or RP73870. Other rats were subjected to pylorus ligation. YM022 and RP73870 inhibited the gastrin-induced acid secretion in a dose- and time-dependent manner; maximal inhibition was observed at a dose of 0.3 mumol.kg-1.hr-1 for both YM022 and RP73870, the ID50 values being 0.02 mumol.kg-1.hr-1 and 0.05 mumol.kg-1.hr-1 for YM022 and RP7870, respectively. At a dose of 0.3 mumol.kg-1.hr-1 YM022 and RP73870 failed to inhibit basal and histamine-, bethanechol-, and insulin-evoked secretion. They also failed to affect the secretion evoked by infusion of a cocktail of maximally effective doses of gastrin-17, histamine and bethanechol. YM022 and RP73870, finally, were without effect on the acid response to pylorus ligation. We suggest that endogenous gastrin in the conscious rat does not contribute to the basal acid secretion and does not participate in the acid response to histamine or to vagus stimulation.

Animals↗