Itzchak Angel - Academia.edu (original) (raw)
Papers by Itzchak Angel
Presynaptic Receptors and Neuronal Transporters, 1991
European Journal of Pharmacology, Dec 30, 1996
We have investigated the effects of 5-hydroxytryptamine (5-HT) on electrically induced contractio... more We have investigated the effects of 5-hydroxytryptamine (5-HT) on electrically induced contractions of rabbit isolated bladder. Electrical field stimulation evoked twitch contractions which were potentiated by 5-HT (0.3 10 l-tM). The potentiating effect of 5-HT was inhibited by ondansetron (pA 2 9.2) and granisetron (pA 2 9,1) but not by methysergide or SB 204070 ((l-butyl-4-piperidinyl)methyl 8-amino-7-chloro-l,4-benzodioxan-5-carboxylate hydrochloride). This suggests that the potentiating effect of micromolar concentrations of 5-HT on neuromuscular transmission in rabbit isolated bladder is mediated by 5-HT 3 receptors. The receptors involved in the response to lower concentrations of 5-HT, observed in some tissues, remain to be characterised.
European Journal of Pharmacology, 1985
Life Sciences, Feb 1, 1997
Contractile responses induced by carbachol on the detrusor muscle and by noradrenaline on the iso... more Contractile responses induced by carbachol on the detrusor muscle and by noradrenaline on the isolated urethra were compared between ovariectomized rats pretreated with estradiol (50 pg/ animal S.C. twice daily for five days), untreated ovariectomized rats and intact animals. In the detrusor muscle, contractions induced by 30pM carbachol, when normalized with respect to KC1 100 mM-induced contraction, were similar for the three groups. Furthermore, contractions induced by 100 ~.IM noradrenaline in the isolated urethra were not significatively different between groups. However, the pDZ value for noradrenaline was greater in urethral tissue from ovariectomized rats compared with ovariectomized-estrogen treated and control rats. A similar result was found for pD, values for carbachol-induced contractions on the detrusor muscle. These results suggest that ovariectomy increases the sensitivity of the urinary bladder and urethra to the contractile effects of carbachol and noradrenaline, respectively and that this effect is reversed by in vivo estrogen pretreatment. Q 1997 Elsevier Science Inc.
![Research paper thumbnail of Regulation of [3H]mazindol binding to subhypothalamic areas: Involvement in glucoprivic feeding](https://attachments.academia-assets.com/71037175/thumbnails/1.jpg)
](Brain Res Bull, 1986
The distribution of low-affinity sodium-sensitive binding sites of [3H]mazindol were studied in r... more The distribution of low-affinity sodium-sensitive binding sites of [3H]mazindol were studied in rat hypothalamic nuclei. Using microdissection methods, it was demonstrated that the highest level of [3H]mazindol binding is localized to the paraventricular nucleus (PVN) and the lowest binding is observed in the lateral hypothalamus. Following food deprivation, a significant decrease in [3H]mazindol binding in the PVN and ventromedial hypothalamus (VHM) were observed. Refeeding food-deprived rats resulted in restoration of the level of binding in the PVN, and this was correlated with changes in blood glucose levels. Thus, changes in the binding of [3H]mazindol in the PVN may reflect local changes in glucose levels. In related studies, the involvement of the PVN in the regulation of food deprivation or 2-deoxyglucose (2-DG)-induced food intake was studied. Application of amphetamine (20 pg) into the PVN had no effect on food deprivation induced feeding, but significantly inhibited 2-DG induced (glucoprivic) feeding. The PVN may play an important role in the glucostatic regulation of feeding and in mediating the anorectic action of amphetamine and related anorectic drugs on glucoprivic feeding. Hypothalamus Anoretic drugs Glucoprivic feeding Paraventricular nucleus [3H]Mazindol binding Amphetamine
Brain Research, 1989
The effects of intracerebroventricular administration of 6-hydroxydopamine (6-OHDA) and 5,7-dihyd... more The effects of intracerebroventricular administration of 6-hydroxydopamine (6-OHDA) and 5,7-dihydroxytryptamine (5,7-DHT) on sodium-sensitive [3H]mazindol binding were investigated in the rat hypothalamus and corpus striatum. In the hypothalamus, specific [3H]mazindol binding was inhibited by low concentrations of sodium and stimulated by high-sodium concentrations, whereas in the corpus striatum, only a sodium-dependent stimulation of [3H]mazindol binding was observed. Lesions with 6-OHDA significantly reduced sodium-dependent [3H]mazindol binding in the corpus striatum, but had no effect on the binding of [3H]mazindol in the absence of sodium. Lesions of serotonergic neurons with 5,7-DHT, however, had no effect on [3H]mazindol binding in the striatum, but resulted in a significant increase in the number of [3H]mazindol binding sites in the hypothalamus. These data suggest that [3H]mazindol may bind to two anatomically distinct binding sites, one that is stimulated and the other inhibited by sodium. The sodium-stimulated binding sites appear to be located on dopaminergic terminals in the striatum, and in the hypothalamus, the sodium-inhibited sites appear to be regulated by serotonergic neuronal activity.
Clinical Neuropharmacology, 1990
Journal of neural transmission. Supplementum
The presynaptic terminal autoreceptors which modulate the release of noradrenaline through a nega... more The presynaptic terminal autoreceptors which modulate the release of noradrenaline through a negative feed-back mechanism correspond to the alpha 2-subtype of adrenoceptors. These receptors are also present post-synaptically in the pancreatic islets were they mediate inhibition of the glucose-induced release of insulin. The sympathetic innervation of the pancreatic islets involves alpha 2-adrenoceptors both presynaptically as well as postsynaptically. SL 84.0418 is a novel alpha 2-adrenoceptor antagonist with preferential effects in the periphery and with at least a 10-fold higher selectivity ratio between alpha 2 and alpha 1-adrenoceptors when compared with idazoxan. SL 84.0418 antagonizes the hyperglycemia and the inhibition of insulin release induced by the alpha 2-adrenoceptor agonist UK 14304. The administration of SL 84.0418 significantly reduces the glucose evoked hyperglycemia in several species including man. It is proposed that SL 84.0418 may represent a useful and novel hypoglycemic drug in the treatment of type II diabetes.
Journal of Pharmacology and Experimental Therapeutics
ABSTRACT
Journal of Pharmacology and Experimental Therapeutics
ABSTRACT
Journal of Pharmacology and Experimental Therapeutics
The selective alpha-2 adrenoceptor agonist UK 14.304 induced in the mouse a dose-dependent hyperg... more The selective alpha-2 adrenoceptor agonist UK 14.304 induced in the mouse a dose-dependent hyperglycemic response which was accompanied by a concomitant inhibition of insulin secretion. Similar effects were observed with the preferential alpha-2 receptor agonists clonidine and guanabenz whereas less pronounced effects were found with (-)-epinephrine. No significant effects on blood glucose levels were observed with the alpha-1 adrenoceptor agonist methoxamine. Adrenalectomy or depletion of catecholamine stores by reserpine, alpha-methylparatyrosine or DSP4 failed to modify the hyperglycemic response to UK 14.304. However, streptozotocin diabetic mice did not respond to UK 14.304. The hyperglycemia induced by submaximal doses of UK 14.304 was antagonized by the centrally and peripherally acting alpha-2 adrenoceptor antagonists rauwolscine, yohimbine, idazoxan and phentolamine, by the peripheral antagonist benextramine but not by prazosin (alpha-1 selective) or propranolol (beta adrenergic). Thus, it may be suggested that the alpha agonist-induced hyperglycemia is mediated via postsynaptic alpha-2 adrenoceptors located on pancreatic beta cells and that it is mediated through the inhibition of insulin secretion.
Preincubation of rat hypothalamic slices in glucose-free Krebs-Ringer buffer (37°C) resulted in ... more Preincubation of rat hypothalamic slices in glucose-free Krebs-Ringer buffer (37°C) resulted in a time-dependent decrease in specific (+)-(³H)amphetamine binding in the crude synaptosomal fraction prepared from these slices. The addition of D-glucose resulted in a dose- and time-dependent stimulation of (+)-(³H)amphetamine binding, whereas incubations with L-glucose, 2-deoxy-D-glucose, or 3-O-methyl-D-glucose failed to increase the number of (+)-(³H)amphetamine binding sites. Ouabain potently inhibited the glucose-induced stimulation of (+)-(³H)amphetamine binding, suggesting the involvement of Na/sup +/, K/sup +/-ATPase. Preincubation of hypothalamic slices with glucose also resulted in an increase in Na/sup +/,K/sup +/-ATPase activity and the number of specific high-affinity binding sites for (³H)ouabain, and a good correlation was observed between the glucose-stimulated increase in (+)-(³H)amphetamine and (³H)ouabain binding. These data suggest that the (+)-(³H)amphetamine binding site in hypothalamus, previously linked to the anorectic actions of various phenylethylamines, is regulated both in vitro and in vivo by physiological concentrations of glucose. Glucose and amphetamine appear to interact at common sites in the hypothalamus to stimulate Na/sup +/,K/sup +/-ATPase activity, and the latter may be involved in the glucostatic regulation of appetite.
Presynaptic Receptors and Neuronal Transporters, 1991
European Journal of Pharmacology, Dec 30, 1996
We have investigated the effects of 5-hydroxytryptamine (5-HT) on electrically induced contractio... more We have investigated the effects of 5-hydroxytryptamine (5-HT) on electrically induced contractions of rabbit isolated bladder. Electrical field stimulation evoked twitch contractions which were potentiated by 5-HT (0.3 10 l-tM). The potentiating effect of 5-HT was inhibited by ondansetron (pA 2 9.2) and granisetron (pA 2 9,1) but not by methysergide or SB 204070 ((l-butyl-4-piperidinyl)methyl 8-amino-7-chloro-l,4-benzodioxan-5-carboxylate hydrochloride). This suggests that the potentiating effect of micromolar concentrations of 5-HT on neuromuscular transmission in rabbit isolated bladder is mediated by 5-HT 3 receptors. The receptors involved in the response to lower concentrations of 5-HT, observed in some tissues, remain to be characterised.
European Journal of Pharmacology, 1985
Life Sciences, Feb 1, 1997
Contractile responses induced by carbachol on the detrusor muscle and by noradrenaline on the iso... more Contractile responses induced by carbachol on the detrusor muscle and by noradrenaline on the isolated urethra were compared between ovariectomized rats pretreated with estradiol (50 pg/ animal S.C. twice daily for five days), untreated ovariectomized rats and intact animals. In the detrusor muscle, contractions induced by 30pM carbachol, when normalized with respect to KC1 100 mM-induced contraction, were similar for the three groups. Furthermore, contractions induced by 100 ~.IM noradrenaline in the isolated urethra were not significatively different between groups. However, the pDZ value for noradrenaline was greater in urethral tissue from ovariectomized rats compared with ovariectomized-estrogen treated and control rats. A similar result was found for pD, values for carbachol-induced contractions on the detrusor muscle. These results suggest that ovariectomy increases the sensitivity of the urinary bladder and urethra to the contractile effects of carbachol and noradrenaline, respectively and that this effect is reversed by in vivo estrogen pretreatment. Q 1997 Elsevier Science Inc.
Brain Res Bull, 1986
The distribution of low-affinity sodium-sensitive binding sites of [3H]mazindol were studied in r... more The distribution of low-affinity sodium-sensitive binding sites of [3H]mazindol were studied in rat hypothalamic nuclei. Using microdissection methods, it was demonstrated that the highest level of [3H]mazindol binding is localized to the paraventricular nucleus (PVN) and the lowest binding is observed in the lateral hypothalamus. Following food deprivation, a significant decrease in [3H]mazindol binding in the PVN and ventromedial hypothalamus (VHM) were observed. Refeeding food-deprived rats resulted in restoration of the level of binding in the PVN, and this was correlated with changes in blood glucose levels. Thus, changes in the binding of [3H]mazindol in the PVN may reflect local changes in glucose levels. In related studies, the involvement of the PVN in the regulation of food deprivation or 2-deoxyglucose (2-DG)-induced food intake was studied. Application of amphetamine (20 pg) into the PVN had no effect on food deprivation induced feeding, but significantly inhibited 2-DG induced (glucoprivic) feeding. The PVN may play an important role in the glucostatic regulation of feeding and in mediating the anorectic action of amphetamine and related anorectic drugs on glucoprivic feeding. Hypothalamus Anoretic drugs Glucoprivic feeding Paraventricular nucleus [3H]Mazindol binding Amphetamine
Brain Research, 1989
The effects of intracerebroventricular administration of 6-hydroxydopamine (6-OHDA) and 5,7-dihyd... more The effects of intracerebroventricular administration of 6-hydroxydopamine (6-OHDA) and 5,7-dihydroxytryptamine (5,7-DHT) on sodium-sensitive [3H]mazindol binding were investigated in the rat hypothalamus and corpus striatum. In the hypothalamus, specific [3H]mazindol binding was inhibited by low concentrations of sodium and stimulated by high-sodium concentrations, whereas in the corpus striatum, only a sodium-dependent stimulation of [3H]mazindol binding was observed. Lesions with 6-OHDA significantly reduced sodium-dependent [3H]mazindol binding in the corpus striatum, but had no effect on the binding of [3H]mazindol in the absence of sodium. Lesions of serotonergic neurons with 5,7-DHT, however, had no effect on [3H]mazindol binding in the striatum, but resulted in a significant increase in the number of [3H]mazindol binding sites in the hypothalamus. These data suggest that [3H]mazindol may bind to two anatomically distinct binding sites, one that is stimulated and the other inhibited by sodium. The sodium-stimulated binding sites appear to be located on dopaminergic terminals in the striatum, and in the hypothalamus, the sodium-inhibited sites appear to be regulated by serotonergic neuronal activity.
Clinical Neuropharmacology, 1990
Journal of neural transmission. Supplementum
The presynaptic terminal autoreceptors which modulate the release of noradrenaline through a nega... more The presynaptic terminal autoreceptors which modulate the release of noradrenaline through a negative feed-back mechanism correspond to the alpha 2-subtype of adrenoceptors. These receptors are also present post-synaptically in the pancreatic islets were they mediate inhibition of the glucose-induced release of insulin. The sympathetic innervation of the pancreatic islets involves alpha 2-adrenoceptors both presynaptically as well as postsynaptically. SL 84.0418 is a novel alpha 2-adrenoceptor antagonist with preferential effects in the periphery and with at least a 10-fold higher selectivity ratio between alpha 2 and alpha 1-adrenoceptors when compared with idazoxan. SL 84.0418 antagonizes the hyperglycemia and the inhibition of insulin release induced by the alpha 2-adrenoceptor agonist UK 14304. The administration of SL 84.0418 significantly reduces the glucose evoked hyperglycemia in several species including man. It is proposed that SL 84.0418 may represent a useful and novel hypoglycemic drug in the treatment of type II diabetes.
Journal of Pharmacology and Experimental Therapeutics
ABSTRACT
Journal of Pharmacology and Experimental Therapeutics
ABSTRACT
Journal of Pharmacology and Experimental Therapeutics
The selective alpha-2 adrenoceptor agonist UK 14.304 induced in the mouse a dose-dependent hyperg... more The selective alpha-2 adrenoceptor agonist UK 14.304 induced in the mouse a dose-dependent hyperglycemic response which was accompanied by a concomitant inhibition of insulin secretion. Similar effects were observed with the preferential alpha-2 receptor agonists clonidine and guanabenz whereas less pronounced effects were found with (-)-epinephrine. No significant effects on blood glucose levels were observed with the alpha-1 adrenoceptor agonist methoxamine. Adrenalectomy or depletion of catecholamine stores by reserpine, alpha-methylparatyrosine or DSP4 failed to modify the hyperglycemic response to UK 14.304. However, streptozotocin diabetic mice did not respond to UK 14.304. The hyperglycemia induced by submaximal doses of UK 14.304 was antagonized by the centrally and peripherally acting alpha-2 adrenoceptor antagonists rauwolscine, yohimbine, idazoxan and phentolamine, by the peripheral antagonist benextramine but not by prazosin (alpha-1 selective) or propranolol (beta adrenergic). Thus, it may be suggested that the alpha agonist-induced hyperglycemia is mediated via postsynaptic alpha-2 adrenoceptors located on pancreatic beta cells and that it is mediated through the inhibition of insulin secretion.
Preincubation of rat hypothalamic slices in glucose-free Krebs-Ringer buffer (37°C) resulted in ... more Preincubation of rat hypothalamic slices in glucose-free Krebs-Ringer buffer (37°C) resulted in a time-dependent decrease in specific (+)-(³H)amphetamine binding in the crude synaptosomal fraction prepared from these slices. The addition of D-glucose resulted in a dose- and time-dependent stimulation of (+)-(³H)amphetamine binding, whereas incubations with L-glucose, 2-deoxy-D-glucose, or 3-O-methyl-D-glucose failed to increase the number of (+)-(³H)amphetamine binding sites. Ouabain potently inhibited the glucose-induced stimulation of (+)-(³H)amphetamine binding, suggesting the involvement of Na/sup +/, K/sup +/-ATPase. Preincubation of hypothalamic slices with glucose also resulted in an increase in Na/sup +/,K/sup +/-ATPase activity and the number of specific high-affinity binding sites for (³H)ouabain, and a good correlation was observed between the glucose-stimulated increase in (+)-(³H)amphetamine and (³H)ouabain binding. These data suggest that the (+)-(³H)amphetamine binding site in hypothalamus, previously linked to the anorectic actions of various phenylethylamines, is regulated both in vitro and in vivo by physiological concentrations of glucose. Glucose and amphetamine appear to interact at common sites in the hypothalamus to stimulate Na/sup +/,K/sup +/-ATPase activity, and the latter may be involved in the glucostatic regulation of appetite.