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Biomedical subjects

F Honda

Publications and source records attributed to F Honda.

33 records · Page 2Linked to original sources
PubMed1979

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↗
PubMed1979

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↗
PubMed1979

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↗
PubMed1979

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↗
PubMed1979

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↗
PubMed1977

Effect of isoprenaline and phenylephrine on the adenosine 3',5'-monophosphate content and mechanical activity of cold-stored and fresh taenia caecum from the guinea-pig.

1. Cold storage treatment of the guinea-pig taenia caecum had a greater inhibitory effect on the isoprenaline-induced relaxation than that induced by phenylephrine. Prolonged cold storage (12-14 days) almost abolished the effect of isoprenaline but only reduced the phenylephrine effect. The ED50 of cyclic adenosine 3',5'-monophosphate (cyclic AMP) that elicited muscle relaxation was not altered by the prolonged cold storage. 2. After cold storage treatment, tissue cyclic AMP content was decreased; however, isoprenaline still caused a dose-dependent increase in the cyclic AMP level. The threshold dose of isoprenaline for cyclic AMP accumulation was the same in fresh and cold-stored preparations. 3. In the fresh preparation, the onset of the isoprenaline (10(-6)M)-induced relaxation preceded the increase in tissue cyclic AMP. 4. Isoprenaline, phenylephrine, adrenaline and noradrenaline at doses (ED50) sufficient to induce muscle relaxation did not always increase the cyclic AMP level. 5. Similarly, the responses to papaverine and nitroglycerine were not accompanied by an increase in cyclic AMP. 6. The adenylate cyclase and phosphodiesterase (low and high Km) activities of taenia caecum were not attenuated by the prolonged cold storage. 7. Propranolol inhibited both the isoprenaline-induced relazation and cyclic AMP accumulation; however, the pA2 values were significantly different for the two events. 8. Based on these results, both the relaxation and cyclic AMP accumulation caused by isoprenaline are mediated by activation of beta-adrenoceptors but are independent phenomena.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1977

Dopamine receptor blocking activity of sulpiride in the central nervous system.

Effects of sulpiride on the central nervous system were studied in catalepsy induction (I) and antagonism to gnawing behaviour (II) induced by apomorphine and methamphetamine in normal rats, and in antagonism to rotational behaviour (III) induced by apomorphine and methamphetamine in rats with substantia nigra unilaterally lesioned chronically by microinjection of 6-hydroxydopamine. Sulpiride was administered orally and intraventricularly, and the effects of sulpiride were compared to those of haloperidol and chlorpromazine administered through the same routes. In oral administration, sulpiride was almost inactive in (I), and was several hundreds to a thousand times less potent than haloperidol in (II) and (III), while chlorpromazine was 20 to 150 times stronger than sulpiride. In intraventricular administration, sulpiride was almost equipotent to haloperidol in (I), and was equally effective to or 2 to 3 times more effective than halopridol in (III), although several times less in all respects. These findings suggest that sulpiride is essentially a potent inhibitory substance on dopamine receptors in the central nervous system and the rather weak central effects of peripherally given sulpiride are due to poor penetration through the blood brain barrier.

Administration, Oral↗
PubMed1977

Local specificity in responses of canine coronary vessels to oxygen deficiency and antianginal drugs.

Influence of oxygen deficiency and vasodilating drugs on coronary arterial tonus was investigated. In the fibrillating heart, hypoxia initially decreased total coronary resistance, later increased it, and exerted little effect on large coronary arteries. Dilation of helically cut specimens of the small coronary arteries occurred more readily than observed in large arteries in response to N2 bubbling or KCN. In the small arteries, the mitochondrial population was more numerous in cellular units and succinic dehydrogenase activity was greater, suggesting that these vessels are more dependent on aerobic metabolism for the maintenance of integrity. Nitrate vasodilators relaxed selectively the large arteries, while adenosine, prenylamine and carbochromen dilated preferentially the small arteries. Dipyridamole, iproveratril, papaverine and propranolol relaxed both arteries equally; however, except for propranolol, these drugs produced preferential relaxation of the small vessels in the fibrillating hearts.

Adenosine↗
PubMed1976

Adenosine 3',5'-cyclic monophosphate as a possible mediator of rotational behaviour induced by dopaminergic receptor stimulation in rats lesioned unilaterally in the substantia nigra.

A possible involvement of c-AMP in the rotational behaviour induced by a stimulation of dopamine receptors in corpus striatum of rats was investigated. Rats were lesioned unilaterally in the substantia nigra with 6-hydroxydopamine. Intraventricular injection of dopamine, norepinephrine and apomorphine induced rotational behaviour towards the intact side as did dibutyryl c-AMP (dB-c-AMP). Dopamine, norepinephrine and apomorphine could activate adenylate cyclase in homogenates of caudate nucleus. The activation by dopamine was blocked by haloperidol. I.p. injected apomorphine increased c-AMP content bilaterally in caudate nucleus and caused turning towards the intact side; theophylline potentiated and haloperidol blocked the effect. In non-lesioned rats, dopamine and norepinephrine, when injected unilaterally into the caudate nucleus, elicited truning twoards the non-injected side if the rats were pretreated with reserpine and tranylcypromine. c-AMP and dB-c-AMP given similarly to rats pretreated with theophylline also produced turning towards the non-injected side regardless the pretreatment with reserpine and tranylcypromine. All these results emphasize the possibility that c-AMP acts as a second messenger in the central dopaminergic pathway in rats. The supersensitivity of the dopaminergic system which developed after denervation is also discussed.

Adenylyl Cyclases↗