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Biomedical subjects

F Honda

Publications and source records attributed to F Honda.

At least 19 recordsLinked to original sources

[Experimental study on local cooling of the eyeball in ocular surgery (4). The local cooling effect on uveal blood circulation, intraocular pressure, and intravitreous pressure].

The effects of local cooling on the uveal blood circulation, intraocular pressure, and intravitreous pressure were evaluated. Saline solutions maintained at 10 degrees C and 35 degrees C were dripped on the rabbit ocular surface. After 5-minute dripping of 10 degrees C saline solution, the temperature decreased by 10.6 degrees C at the ciliary body, 7.7 degrees C at the choroid and 2.9 degrees C at the central region of the vitreous. Hydrogen clearance with electrolytically generated hydrogen gas was employed to measure the tissue blood flow, which fell to 82.9% of normo-thermal value at the ciliary body and 86.3% at the choroid. The intravitreous pressure dropped by 2.8 mmHg. After 30-minute dripping of 10 degrees C saline solution, the intraocular pressure dropped by 3.0 mmHg. We consider that the reduction of intraocular and intravitreous pressure during local cooling of the ocular surface is related to decrease in the uveal blood flow.

Animals

[The local cooling effect of anterior chamber irrigation on the blood-aqueous barrier].

Local cooling effect on the breakdown of the blood-aqueous barrier (BAB) following anterior chamber irrigation, including additional direct irritation of the iris, was evaluated fluorophotometrically. The rabbit anterior chamber was irrigated with simulated aqueous humor (S-MA 2) the temperature of which was maintained at 35 degrees C or 10 degrees C. The fluorophotometry was performed before and 4, 24, 48 hours and 7 days after irrigation for 30 or 60 minutes. The temperature changes in the anterior chamber, retrolental vitreous body and posterior retina were also measured with a thermocouple during irrigation at 10 degrees C. The temperature of the anterior chamber and the retrolental vitreous fell to 15.0 degrees C and 28.2 degrees C, respectively, within 30 minutes after starting irrigation, whereas the temperature drop in the posterior retina was only 2.0 degrees C after 60 min. At 4 hours after 60-minute irrigation, the breakdown of the BAB was greater than following 30-minute irrigation. There was no significant difference in the BAB breakdown between eyes irrigated at 10 degrees C and 35 degrees C.

Animals

Backward walking induced by L-5-hydroxytryptophan in mice.

An intraperitoneal administration of large doses of L-5-hydroxytryptophan (L-5HTP) induced dose-dependently a behaviour characterized by backward walking in mice. D-5-hydroxytryptophan (D-5HTP) and L-3,4-dihydroxyphenylalanine (L-DOPA) in the same doses failed to induce such behaviour. The backward walking induced by L-5HTP was blocked by a decarboxylase inhibitor, DL-alpha-methyl-DOPA, but was potentiated by a monoamine oxidase inhibitor (MAOI), tranylcypromine or pargyline. An intracerebral injection of L-5-hydroxytryptamine (5-HT) induced a similar backward walking which was potentiated by a MAOI. The backward walking induced by L-5HTP was completely inhibited by 5-HT and dopamine (DA) receptor blockers, but was not inhibited by alpha- or beta-adrenergic blocker, antihistamine or anticholinergic drug. On the other hand, zimelidine and clomipramine, 5-HT uptake inhibitors, markedly potentiated the backward walking, while desipramine had no effect. From the results, it appears that excess amounts of 5-HT formed from L-5HTP produced the backward walking by directly stimulating the central 5-HT receptors, and DA is also involved in the behaviour. This behaviour may serve as a good model to assess the central serotonergic activity of drugs.

5-Hydroxytryptophan

A simple histochemical screening method for amine uptake.

A simple histochemical method for screening amine uptake in vitro is described. The filum terminale and the Vibratome sections of the caudate nucleus of reserpinized rats were used as the sources of noradrenaline (NA) and 5-hydroxytryptamine (5-HT), and as the sources of dopamine (DA) containing neurons, respectively. When incubated in an oxygenated medium (Krebs-Ringer) containing the corresponding amines, these preparations effectively accumulated the amines. 6-Hydroxytryptamine (6-HT) was used instead of 5-HT because of its stronger fluorescence and lower photo-decomposition of beta-carboline formed from 6-HT. The inhibitory patterns of representative uptake inhibitors obtained by the present method agreed well with those reported previously by biochemical methods. Effects of other types of drugs were also studied. The present method is a simple, rapid and non-radioisotopic method for determining amine uptake inhibiting action of a drug and the degree and selectivity in which it acts on the three kinds of amines.

Animals

Dopamine receptor blocking activity of sulpiride in the canine exocrine pancreas.

The inhibitory effect of sulpiride on dopamine receptors was investigated in the exocrine pancreas of dogs anesthetized with pentobarbital and with the stomach ligated at the pylorus. All test substances were given intravenously. Dopamine, acetylcholine, histamine and secretin produced a dose-related increase in pancreatic juice secretion, though the dose-effect curves of these secretagogues differed in shape. Epinephrine, norepinephrine, isoproterenol, methamphetamine and serotonin had no secretagogue effects. The effects of acetylcholine and histamine were inhibited by atropine and cimetidine, respectively. The effect of dopamine was blocked by haloperidol, but not by atropine, cimetidine, phentolamine and propranolol. These results suggest that dopamine acts on specific dopamine receptors related to the exocrine pancreatic secretion. Haloperidol had no effect on the effects of acetylcholine and histamine, but did inhibit the secretin-induced secretion, though the inhibitory effect was to a lesser extent than on the dopamine response. Sulpiride and chlorpromazine also suppressed dose-dependently the dopamine-induced secretion. The inhibitory activity of sulpiride was almost the same as that of haloperidol, and 12 times more potent than that of chlorpromazine. Sulpiride was found to be a potent dopamine antagonist in the canine exocrine pancreas.

Acetylcholine

Role of brain amines in the fetal hyperpyrexia caused by tranylcypromine in LiCl-pretreated rats.

Tranylcypromine (TCP), a monoamine oxidase inhibitor, caused a fatal hyperpyrexia in rats pretreated with LiCl once a day for 4 days. Pretreatment with LiCl alone did not alter the level of serotonin (5-HT), dopamine (DA) and norepinephrine (NE) in the brain. In fatal hyperpyrexia caused by LiCl plus TCP, the brain 5-HT and DA levels were increased, whereas the brain NE level was decreased. Reserpine and alpha-methyl-p-tyrosine completely prevented the hyperpyrexia, but FLA-63 did not show any effect. The hyperpyrexia was completely prevented by p-chlorophenylalanine (PCPA) given 72 hours before TCP but not by PCPA given 24 hours before TCP. Haloperidol and chlorpromazine, DA receptor blockers, inhibited the fatal hyperpyrexia, while cyproheptadine and methysergide, 5-HT receptor blockers, did not. These results suggest that DA plays an essential role in the hyperpyrexia induced by the combination of TCP and LiCl in rats, but the involvement of 5-HT is inconclusive.

Amines

Amines and the rat exocrine pancreas: (1). Effects of receptor blockers on turnover of L-dopa.

The acinar cells of the exocrine pancreas have the capacity of efficiently take up and metabolize L-dopa. In the present study, the metabolism of L-dopa by the exocrine pancreas of the rat and effects of receptor blockers on the metabolism were studied by fluorescent histochemical and chemical methods. After i.v. administration of L-dopa (50 mg/kg), a large amount of dopamine (DA) was detected in the exocrine pancreas, and in the pancreatic juice large amounts of DA and its metabolites. DA-blockers (haloperidol, sulpiride, and pimozide) and alpha-blockers (phenoxybenzamine, and phentolamine) produced a significant increase in the accumulation of DA after administration of L-dopa. On the other hand, beta-blockers (propranolol, and oxprenolol) were without effects. The excretion of DA into the pancreatic juice appeared to be associated with the secretion of zymogen granules, thus DA serves as an indicator of pancreatic secretory activity, especially of enzyme secretion. Because DA- and alpha-blockers produced an increase in the accumulation of DA, dopaminergic and/or alpha-adrenergic mechanisms probably exist in the exocrine pancreas of the rat and these mechanisms modify the enzyme secretion.

Adrenergic alpha-Antagonists

Amines and the rat exocrine pancreas: (2) Effects of receptor blockers on turnover of L-5HTP.

The metabolism of L-5HTP by the rat exocrine pancreas, and effects of blockers on the metabolism were studied by fluorescent histochemical and chemical methods. Histochemically, 5-hydroxytryptamine (5-HT) blockers (methyserigide and cyprohepatdine) and dopamine (DA) blockers (haloperidol and sulpiride) produced no apparent changes in fluorescence pictures after injection of L-5HTP. alpha-blockers (phenoxybenzamine and phentolamine) and monoamine oxidase (MAO) inhibitor (iproniazide) produced an increased accumulation of 5-HT fluorescence in the apical regions of acinar cells where the zymogen granules are stored. Chemically, the 5-HT blockers decreased the 5-HT content after injection of L-5HPT. Sulpiride had no effect. Haloperidol decreased the 5-HT content. MAO inhibitor resulted in a vast accumulation of L-dopa: e.g. (1) L-5HTP was more slowly eliminated, and (2) 5-HT blockers produced a decreased content of 5-HT after injection of L-5HTP, in contrast to the finding that DA-blockers produced an incresed content of DA after injection of L-dopa. The mechanism responsible for the differences is discussed in relation to the possible pharmacological effects of L-5HTP and L-dopa on the secretion from the exocrine pancreas of rats.

5-Hydroxytryptophan

Amines and the rat exocrine pancreas: (3) Effects of amines on pancreatic secretion.

Effects of L-dopa, L-5HTP, a few amines, and related compounds on the pancreatic rate of flow, protein secretion, and bicarbonate secretion were studied in conscious rats. Single injections of L-dopa, DA and apomorphine did not modify the rate of flow, while an increase was seen with infusion of DA. L-dopa stimulated the protein secretion. L-5HTP and 5-HT decreased the rate of flow and protein secretion. Effects of L-dopa and L-5HTP on the protein secretion were prevented by DA- and 5-HT blockers, respectively. Neither L-dopa nor L-5HTP had any effect on the bicarbonate secretion. Secretin and cholinergic agents (acetylcholine and carbamylcholine) strongly stimulated the rate of flow of pancreatic juice. alpha-Agonists (phenylephrine and clonidine) decreased the rate of flow, and the effects were inhibited by an alpha-blocker. The alpha-agonists had no effect on protein secretion. Although, alpha-blockers (phenoxybenzamine and phentolamine) had no effects on the rate of flow, they did decrease the protein secretion. Isoproterenol was a potent secretagogue, and the effect was suppressed by a beta-blocker. Histamine had no effect on the rate of flow. The results were discussed in relation to our previous histochemical and chemical findings, and the species difference between rats and dogs in response to the amines.

5-Hydroxytryptophan

Pharmacological study of [2-chloro-11-(2-dimethylaminoethoxy) dibenzo[b,f]thiepine] (zotepine), a new neuroleptic drug.

2-Chloro-11-(2-dimethyl-aminoethoxy)dibenzo [b,f]thiepine (zotepine) is a new neuroleptic drug with a chemical structure different from known neuroleptics. The psychopharmacological effects of zotepine in mice, rats and dogs were studied and compared with those of commercially available neuroleptics. Haloperidol and perphenazine were the most active and thioridazine was the least active in hibiting apomorphine-induced gnawing and circling movement, methamphetamine-induced gnawing and circling movement, conditioned avoidance response, motor activity, dopamine-induced pancreatic secretion and apomorphine-induced vomiting. These drugs also had the same order of potency in inducing catalepsy and increasing dopamine turnover and prolactin release. Chlorpromazine, propericiazine and thiothixene were intermediate in potency. Zotepine equalled chlorpromazine in most activities, however, it was clearly less active than chlorpromazine in potentiation of barbiturate sleep and cardiovascular effect.

Animals