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Biomedical subjects

J Bugajski

Publications and source records attributed to J Bugajski.

88 records · Page 5Linked to original sources
PubMed1976

Effect of metiamide, a histamine H2 - receptor antagonist, on the development of gastric stress ulcers and acid secretion.

In normal and stressed rats with chronic gastric fistula small doses of metiamide (0.001-0.01 muM/kg) increased and doses of over 20 muM/kg decreased gastric acid secretion. In both these dose ranges of dosage metiamide suppressed the development of stress ulcers, most markedly in doses of 0.005 and 100 muM/kg. Intermediate doses had no such action. Only the anti-ulcer action of large doses of metiamide ran parallel to a reduction in acid secretion. Small doses of metiamide increased gastric secretion, but like larger doses, had a weak adrenergic action.

Animals↗
PubMed1976

Effect of adrenergic blockade on gastric secretion altered by catecholamines in rats.

The effect of adrenergic blockade on gastric secretion altered by catecholamines was studied for 4 hr after injection in rats with chronic gastric fistulas. The alpha-adrenergic blockers phenoxybenzamine and phentolamine significantly inhibited the basal secretion of HCl and pepsin. Blockade of the beta-adrenergic receptors with propranolol did not change this secretion. Practolol in small doses slightly increased and in larger doses inhibited HCl out-put. Of the catecholamines, adrenaline and dopamine most markedly reduced HCl and pepsin secretion, while noradrenaline and isoprenaline had a weaker effect. Neither alpha- nor beta-adrenergic blockers prevented the inhibitory action of the catecholamines employed, but intensified the depression of the gastric secretion provoked by them. Adrenergic blockers inhibited secretion after catecholamines as well as basal secretion. This indicates that these two antagonistic groups of compounds act independently on the mechanism controlling gastric secretion. It is unlikely that this takes place indirectly through changes in the blood supply of the gastric mucosa.

Adrenergic alpha-Antagonists↗
PubMed1975

The influence of serotonin on insulin-stimulated gastric secretion, blood glucose and serum electrolyte levels in the unanesthetized rat.

The effect of various doses of serotonin (5-HT) on the basal or insulin-stimulated gastric secretion was studied, for 4 hr after the injection, in unanesthetized rats with chronic gastric fistulas. The blood glucose and serum Na, K and Ca ions concentrations were also determined. Insulin produced hypoglycemia and hypokalemia, most pronounced in the first hr, and increased HCl and pepsin output, with a maximum at 2 hr after the injection. 5-HT significantly inhibited both basal and insulin-stimulated gastric secretion. The amine produced transient hyperglycemia, which was less pronounced in rats simultaneously receiving insulin. The inhibition of insulin-stimulated gastric secretion by 5-HT lasted for a longer period than the prevention of the biochemical changes brought about by insulin. The prevention by 5-HT of insulin hypoglycemia and hypokalemia may be of significant importance in the mechanism of the depression of insulin-stimulated gastric secretion.

Animals↗
PubMedDate not supplied

The effect of neuroleptics on the development of gastric ulcers in rats exposed to restraint-cold stress.

Gastric ulcer development and changes in the contents of glucose, free fatty acids (FFA), and K and Ca ions in the blood were studied in rats subjected to a graded stress of immobilisation and cold. During stress the volume of secretion and the output of HCl, decreased although the concentration rose slightly. Chlorpromazine (CPZ), thioridazine (TRZ), spiroperidol (SPI), and fluphenazine (FLU) inhibited to various degrees ulcer formation during stress. SPI reduced stress-induced mucosal damages in 94%, but FLU even in doses 100 times smaller than those of the other drugs counteracted ulcer formation. CPZ, TRZ and SPI in preventive doses increased proportionally the blood glucose level both in control rats and in those subject to stress. FLU in effective doses produced no hyperglycemia either in control rats or in those exposed to stress. We conclude that the prevention of gastric ulcer development by neuroleptics may be the result of their antisecretory action and counteracting of breakdown of sympathetic activity during severe stress.

Animals↗
PubMedDate not supplied

Effect of brain mast cells degranulation on the corticosterone response to stimulation of central opioid receptors in rats.

The influence of brain mast cells degranulation, exerted by compound 48/80 given intracerebroventricularly, on the opioid-induced stimulation of the pituitary-adrenal axis, measured indirectly through corticosterone secretion, was investigated in conscious rats. The mu- and delta-opioid receptor agonists Leu-enkephalinamide, morphine and beta-endorphin, given intracerebroventricularly, dose-dependently increased the serum corticosterone levels. The effect of Leu-enkephalinamide was not changed by pretreatment with the histamine H1- and H2-receptor antagonists mepyramine and cimetidine. When Leu-enkephalinamide, morphine and beta-endorphin were given 3 hr after compound 48/80, the serum corticosterone levels were higher than after either one of these drugs given separately, which suggests an independent mechanism of action. In rats pretreated 24 hr earlier with compound 48/80, i.e., when brain mast cells were completely degranulated, the stimulating effect of morphine was almost abolished and the effects of Leu-enkephalinamide and beta-endorphin were considerably reduced. Since the histamine levels in the whole brain and thalamus were elevated 3 and 24 hr after administration of compound 48/80, these results suggest that factors other than histamine depletion from brain mast cells by compound 48/80 may be responsible for the dramatic impairment of the stimulating effect of morphine, Leu-enkephalinamide and beta-endorphin on the pituitary-adrenal axis.

Animals↗
PubMedDate not supplied

Effects of neuroleptics on blood glucose, free fatty acids and liver glycogen levels in the rat.

In fed rats the mechanisms of the action of spiroperidol (SPI), chlorpromazine (CPZ), fluphenazine (FLU) and thioridazine (TRZ) blood glucose, liver glycogen, serum free fatty acids (FFA) and K ion levels were investigated. Phenothiazines induced significant hyperglycemic responses with concomitant increase in liver glycogen, elevation of serum FFA and hypokalemia. CPZ and FLU were the most potent and TRZ was least potent in inducing above mentioned metabolic responses, which were most pronounced in 4--6 hr. SPI produced significant hyperglycemia for sorter period of time with a subsequent decrease of liver glycogen. An alpha-adrenergic antagonist, phentolamine prevented neuroleptic-induced hyperglycemia, impaired the increase of liver glycogen, partially diminished hyperlipemia and did not substantially change hypokalema occuring following neuroleptics. Antagonist of beta-adrenergic receptor, propranolol did not practically influence metabolic responses to neuroleptics. Adrenalectomy impaired substantially but did not abolish neuroleptic-induced hyperglycemia, indicating that also extraadrenal mechanisma, conceivable impairing glucose utilization and metabolism, are responsible for hyperglycemia induced by neuroleptics. This experiments suggest that phenothiazines may induce hyperglycemic response by activation of alpha-adrenergic receptors by contrast to alpha-adrenertic blocking action of these drugs in the central nervous system.

Adrenalectomy↗
PubMedDate not supplied

Central metabolic and pituitary-adrenocortical stimulatory action of histamine and clonidine.

This review presents our new findings regarding the centrally-induced effects of histamine and clonidine. We have found for the first time that histamine administered intracerebroventricularly (icv) induces a dose-related increase in serum free fatty acids (FFA) in conscious rats. Both H1 and H2 receptors participate in this stimulation. Histamine interacts with central alpha 1 and beta-adrenoceptors and with cholinergic muscarinic receptors when inducing hyperlipemic response in non-stressed rats. Clonidine given icv induces also hyperlipemia which, as shown by us, is elicited by a central alpha 2-adrenergic mechanism. In hypothermia caused in rats by clonidine not only already known central alpha-adrenergic but also an H2-histaminergic mechanism participates to an equal extent. We have found for the first time that in conscious rats both under normal and stress conditions not only central histamine H1- but also H2-receptors mediate the stimulation of the pituitary-adrenocortical response measured indirectly through corticosterone secretion. In our study evidence has for the first time been obtained that in non-stressed rats brain histaminergic mechanism interacts with alpha 1, alpha 2- and beta-adrenoceptors and with cholinergic muscarinic receptors when stimulating the pituitary-adrenocortical response. By contrast, in stressed animals central histamine H1- and H2-receptors interact with alpha 1- and alpha 2- but not beta-adrenergic and cholinergic muscarinic receptors when increasing the corticosterone response. We have also demonstrated that in contrast to a known inhibitory action on adrenocortical secretion in anesthetized dogs, clonidine given icv increases the corticosterone response in both non-stressed and stressed rats by stimulating alpha-adrenoceptors. In stressed animals this effect of clonidine is also mediated, to an equal extent, by H2-receptor mechanism. Our data strongly suggest that in some central effects clonidine affects both alpha 2 and H2 receptor mechanism. This challenges the view that clonidine is a selective alpha-adrenergic agonist.

Animals↗
PubMedDate not supplied

Effect of adrenergic antagonists on clonidine-induced inhibition of basal gastric secretion in conscious rats.

In unanesthetized rats with chronic gastric fistulas the mechanism of the inhibitory action of clonidine (CLO) on basal gastric secretion was investigated. CLO (0.001-1 mg/kg ip) reduced significantly in a dose-dependent fashion, the basal gastric acid output, and after higher doses no secretion occurred. Noradrenaline (0.1-2.5 mg/kg ip) even in much higher doses was less effective in inhibiting basal gastric secretion in rats. A postsynaptic alpha-adrenergic receptor blocker phenoxybenzamine antagonized only moderately the inhibitory effect of CLO. Phentolamine was more potent in this respect and antagonized significantly, by about a half, the antisecretory effect of CLO. Yohimbine, a presynaptic alpha-adrenoceptor blocker, counteracted insignificantly the inhibitory influence of CLO on basal gastric secretion. The alpha-adrenergic inhibitory receptors in the gastric mucosa, stimulated by CLO, are sensitive to both pre- and post-synaptically acting adrenergic blockers.

Adrenergic alpha-Antagonists↗
PubMedDate not supplied

The effect of drugs interfering with biogenic amines metabolism on gastric secretion and reserpine-ulcers development in rats.

The effect of drugs interfering with endogenous catecholamines metabolism on gastric secretion and gastric ulcers development 4 hr following reserpine administration was investigated in rats with chronic gastric fistulas. Drugs inhibiting catecholamine synthesis: alpha-methyl-p-tyrosine (alpha-MT) and sodium diethyldithiocarbamate (DDC) decreased substantially the reserpine-induced gastric acid and pepsin secretion, but only alpha-MT diminished the development of gastric ulcers. Pretreatment with nialamide (NLD) elicited in reserpinized rats a marked inhibition both of gastric secretion and of gastric ulcers development. Dopamine (DA), noradrenaline (NA) and adrenaline (A) decreased the secretion of hydrochloric acid but did not change the intensity of gastric ulcers caused by reserpine. Desipramine strongly inhibited reserpine-induced gastric acid secretion. Reserpine depleted DA, NA and 5-HT stores in the brain and decreased DA and 5-HT levels in the wall of the stomach in which the NA levels were increased. The changes in biogenic amines content induced by drugs in reserpinized rats did not correlate with their influence on gastric secretion and on the development of mucosal ulcers. The inhibitory effect of all of the drugs examined on gastric acid and pepsin secretion in reserpinized rats was accompanied by the inhibition of gastric ulcers formation following NLD and alpha-MT administration only, indicating that ulcer generation following reserpine depends more on changes in mucosal barrier resistance than on gastric acid secretion.

Animals↗
PubMedDate not supplied

Effect of catecholamines and adrenergic antagonists on blood glucose, free fatty acids and liver glycogen levels in fed rats.

In fed rats the effects of catechloamines and adrenergic antagonists on blood glucose, free fatty acids (FFA), and liver glycogen levels were investigated in order to determine the role of alpha- and beta-adrenergic receptors in metabolic responses to catechloamines. Hyperglycemic responses to dopamine (DA), noradrenaline (NA), adrenaline (A) and isoprenaline (ISP) were dose-related and accompained by a depletion of liver glycogen. The relative potencies in producing hyperglycemia and in causing liver glycogenolysis were in descending order of potency, A, NA, DA and ISP. Hyperlipemic response was most potent to NA and DA, weaker to ISP, and least potent to A. Phentolamine antagonized completely both hyperglycemia and hepatic glycogen depletion induced by all catecholamines. Propranolol impaired only hyperglycemic responses to A and ISP. Phentolamine antagonized hyperlipemia induced by DA and NA but only partially impaired hyperlipemia after A. Propranolol only partially antagonized hyperlipemic responses to NA and ISP without influencing DA--and A-induced hyperlipemia. The results indicate that in fed rats hyperglycemic responses to catecholamines are mediated mainly by an alpha-adrenergic receptor, and hyperlipemic responses do not fit inton the alpha-receptor or beta-receptor classification.

Animals↗