Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: DrugBank:APRD00345 (ICI)
5,388 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

[45Ca2+] Uptake was studied in response to adrenaline, isoprenaline, noradrenaline, and (Bu)2cAMP in platelets from patients with anorexia nervosa. In both controls and anorectics, adrenaline, isoprenaline, noradrenaline, and (Bu)2cAMP stimulated [45Ca2+] uptake. In receptor subtype characterisation studies on control platelets, adrenaline-stimulated [45Ca2+] uptake was blocked by yohimbine (an alpha 2-adrenoceptor antagonist) and the specific beta 2-adrenoceptor antagonist ICI 118,551, but not by atenolol (a beta 1-antagonist). Isoprenaline action was blocked by ICI 118,551, but not by yohimbine. Noradrenaline-stimulated [45Ca2+] uptake was blocked by yohimbine but not by ICI 118,551. In platelets from anorectic patients, there was a significant increase in noradrenaline-stimulated [45Ca2+] uptake, a significant diminution in adrenaline and isoprenaline-stimulated [45Ca2+] uptake, but no significant difference in (Bu)2cAMP-stimulated [45Ca2+] uptake, when compared with controls. Basal uptake was also significantly enhanced in anorectics and was found to be inhibited with verapamil but not adrenoceptor antagonist. These data firstly indicate that both alpha 2- and beta 2-adrenoceptor activation elicits [45Ca2+] uptake by platelets. It is proposed that this stimulated [45Ca2+] uptake does not reflect changes in cytosolic Ca2+ but to localized changes of Ca2+ at the plasma membrane, possibly associated with receptor activation, per se. The respective increase and decrease of alpha- and beta-adrenoceptor activity in platelets from anorectic patients is in accord with other reports of changes of adrenoceptor number and type in platelets and other cells from anorectic patients. There may also be an increase in calcium channel activity in platelets from anorectics.
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PMID:Differential changes in alpha- and beta-adrenoceptor linked [45Ca2+] uptake in platelets from patients with anorexia nervosa. 134 46

The role of hypothalamic paraventricular adrenoceptors and angiotensin II (ANG II)-AT 1 receptors in mediating the vasopressin (AVP) release into the plasma in response to i.c.v. and local paraventricular ANG II injections was investigated in conscious chronically instrumented rats. Noradrenaline (NA) administered bilaterally into the paraventricular nucleus (PVN) dose-dependently stimulated AVP release. Bilateral PVN microinjections of the alpha 1 adrenoceptor agonists methoxamine and phenylephrine, or of the alpha2 adrenoceptor agonist clonidine, did not affect plasma AVP when given alone, but increased plasma AVP when methoxamine and clonidine were given in combination. In contrast, PVN microinjections of both the beta 1 adrenoceptor agonist dobutamine and the beta 2 adrenoceptor agonist salbutamol significantly reduced basal plasma AVP. Bilateral PVN pretreatment with the alpha 1 and alpha 2 adrenergic antagonists prazosin, idazoxan and rauwolscine, but not of the beta 1 and beta 2 adrenoceptor antagonists atenolol and ICI 118 551, significantly attenuated the i.c.v. ANG II-induced AVP release. ANG II injected bilaterally into the PVN dose-dependently increased plasma AVP. Bilateral PVN pretreatment with the specific ANG II-AT 1 receptor antagonist losartan partially inhibited the i.c.v. ANG II-induced AVP release. We conclude: 1) Beta 1 and beta 2 adrenoceptors in the PVN exert an inhibitory action on basal AVP secretion. 2) ANG II can release AVP by directly stimulating its ANG II-AT 1 receptors in the PVN. 3) PVN mediated AVP release in response to periventricular ANG II-AT 1 receptor stimulation is at least partially effected through ANG II-AT 1 receptors in the PVN impinging on alpha adrenergic terminals.
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PMID:Involvement of adrenergic and angiotensinergic receptors in the paraventricular nucleus in the angiotensin II-induced vasopressin release. 146 31

Sympathetic regulation of myocardial performance has been shown to be altered in congestive heart failure. Right atrial tissue of children with severe acyanotic and cyanotic congenital heart disease (CHD) showed a significantly lower beta-receptor density than that of children with less severe defects. Since mononuclear leukocytes (MNL) contain a homogeneous population of beta 2-adrenoceptors which have similar properties to those of cardiac beta 2-adrenoceptors, they are frequently used for studying the beta-adrenergic system. In a group of 37 children with CHD of different types and severity who underwent cardiac surgery, we compared the MNL beta-adrenoceptor density to the type and severity of CHD and looked for a possible relationship to plasma catecholamine levels and to the right atrial beta-adrenoceptor density. Membranes of MNL and myocardial cells were radiolabeled with (-)3-[125I]Iodocyanopindolol [( 125I]ICYP). A significantly higher beta-adrenoceptor density on MNL was found in patients with moderate acyanotic CHD (group I) than in those with severe acyanotic (group II) and cyanotic CHD (group III). Patients of group I showed approximately 50% higher myocardial beta-receptor density than those of groups II and III. ICI 118.551-[125I]ICYP competition studies revealed that in groups II and III significantly lower proportions and densities of beta 1-receptors were found compared to group I. Noradrenaline (NA) plasma levels in group II and group III were significantly higher than those in group I. The adrenaline plasma levels were found to be very high in all children with CHD.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Beta-adrenoceptor density on mononuclear leukocytes and right atrial myocardium in infants and children with congenital heart disease. 166 27

Adrenoceptors mediating relaxant responses to exogenously added or endogenously released catecholamines in isolated canine bronchi (3rd-6th order) were characterized using selective beta receptor agonists and antagonists. Norepinephrine (3 x 10(7) to 3 x 10(-5) M) or isoproterenol (3 x 10(-8) to 10(-6) M) fully relaxed tissues precontracted with 3 x 10(-7) M carbachol (Cch). Salbutamol (Sal) also relaxed Cch-precontracted tissues, but this relaxant effect was extremely sensitive to the concentration of precontracting agent used: the maximal effect of Sal was 100, 79 and 28% reversal of tone in tissues precontracted with 2 x 10(-8), 10(-7) and 3 x 10(-7) M Cch. The effects of isoproterenol were antagonized by propranolol. Norepinephrine relaxations were antagonized by the beta-1-selective antagonist ICI 89,406 (pA2 = 7.70) and the beta-2-selective antagonist ICI 118,551 (pA2 = 6.33). Sal-relaxations were antagonized by ICI 118,551 (pA2 = 8.91). Field stimulation in tissues precontracted with McNeil A343 (M1-selective muscarinic agonist) produced transient relaxations which were antagonized by ICI 89,406 but not ICI 118,551 (both 10(-9) to 10(-7) M). Thus, exogenous and endogenous catecholamines relax canine bronchial smooth muscle by activating both beta-1 and beta-2 adrenoceptors, although the latter seen to play a significant role only when low concentrations of Cch were used.
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PMID:Classification of postjunctional beta adrenoceptors mediating relaxation of canine bronchi. 167

To study the physiologic role of human myocardial beta-2 adrenoceptors, the beta adrenoceptor subtype(s) involved in the effects of catecholamines in vitro on the force of contraction and in vivo on heart rate were characterized. In vitro on both isolated electrically driven right and left atrial and left papillary muscle preparations, isoprenaline and adrenaline caused positive inotropic effects via beta-1 and beta-2 adrenoceptor stimulation. In the atria both beta-1 and beta-2 adrenoceptor stimulation increased contractile force to a maximum; in left papillary muscle, however, only beta-1 adrenoceptor stimulation maximally increased contractile force, whereas beta-2 adrenoceptor stimulation caused only submaximal increases. Noradrenaline, on the other hand, caused a positive inotropic effect nearly exclusively via atrial and ventricular beta-1 adrenoceptor stimulation. In vivo in 10 healthy volunteers isoprenaline-induced tachycardia was antagonized with equal potency by the beta-2 adrenoceptor-selective antagonist ICI 118,551 and the beta-1 adrenoceptor-selective antagonist bisoprolol indicating that it is mediated by cardiac beta-1 and beta-2 adrenoceptor stimulation to about the same degree. In contrast, exercise-induced tachycardia (that is mediated mainly by noradrenaline released from the neurons) was antagonized only by bisoprolol but not by ICI 118,551. It is concluded that in humans under normal physiologic conditions contractility and/or heart rate is regulated only by cardiac beta-1 adrenoceptors. In situations of stress, however, when large amounts of adrenaline are released from the adrenal medulla, stimulation of cardiac beta-2 adrenoceptors could contribute to additional increases in contractility, heart rate, or both.
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PMID:On the physiologic role of beta-2 adrenoceptors in the human heart: in vitro and in vivo studies. 196 97

Cardiovascular and sympathoadrenal effects of short-term oral treatment with beta 1-blockade (atenolol, 50 mg, administered two times) and beta 2-blockade (ICI 118,551, 50 mg, administered three times) were compared with placebo during actual flying in subjects with flight phobia (n = 34). beta 1-Blockade lowered resting blood pressure and heart rate and prevented a heart rate response but not a blood pressure response to this psychologic stress. beta 2-Blockade minimally lowered resting heart rate and prevented a heart rate response, but it failed to lower resting blood pressure or blood pressure response to the stress. Plasma epinephrine increased with all three treatments and more with beta 1-blockade than with placebo. Plasma norepinephrine decreased with administration of beta 2-blockade. Thus neither beta 1- nor beta 2-blockade prevents an increase in blood pressure during acute flight phobia stress. Increased plasma epinephrine seems to be the sympathetic variable that is closest related to this increase in blood pressure. Norepinephrine may be less consistently related to the blood pressure rise during flight phobia stress as shown by the decrease in plasma norepinephrine with administration of beta 2-blockade.
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PMID:Effects of beta 1- and beta 2-blockade on blood pressure and sympathetic responses to flight phobia stress. 197 40

The effect of isoprenaline on cyclic AMP accumulation has been investigated in the rat neuronal cell line B50 and the rat astrocytoma cell line C6. Noradrenaline and isoprenaline stimulated cyclic AMP accumulation in both cell lines. Isoprenaline (0.5 microM; EC50 = 0.1 microM) produced a rapid (T1/2 = 1.3 min) increase in [3H]cyclic AMP accumulation in B50 cells while the response to isoprenaline (0.1 microM; EC50 = 0.01 microM) in C6 cells was somewhat slower (T1/2 = 7.5 min). The response to 0.5 microM isoprenaline was antagonized by both propranolol (IC50 = 8.4 +/- 1.6 nM; N = 3) and the beta 2-selective antagonist ICI 118551 (IC50 = 2.1 +/- 0.2 nM; N = 6). However, no attenuation of the response to isoprenaline (0.5 microM) was observed at concentrations of the beta 1-adrenoceptor antagonist atenolol up to 10 microM (N = 3). In contrast, in C6 cells, which have previously been shown to possess beta 1-adrenoceptors, atenolol inhibited isoprenaline-induced (0.1 microM) cyclic AMP accumulation (IC50 = 2.0 +/- 0.5 microM; N = 6). Furthermore, the beta 2-selective antagonist ICI 118551 was much less potent in the C6 cell line (IC50 = 0.2 +/- 0.05 microM; N = 3) than in the B50 cells. In conclusion, the present data suggest that isoprenaline mediates cyclic AMP accumulation in the neuronal cell line via activation of beta 2-adrenoceptors, while in the astrocytoma cell line the cyclic AMP response is mediated by beta 1-adrenoceptors.
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PMID:Expression of beta 2-adrenoceptors mediating cyclic AMP accumulation in astroglial and neuronal cell lines derived from the rat CNS. 217 29

1. The effects of a six week period of streptozotocin-induced diabetes on tissue catecholamines and on in vivo noradrenaline turnover were assessed in rats. 2. Noradrenaline concentrations measured in heart ventricle, terminal ileum, vas deferens, spleen and adrenal tissue from the diabetic rats were all found to be elevated compared to those found in control rat tissues. The adrenaline contents of the adrenal glands were also raised in these animals. 3. Noradrenaline turnover in heart ventricle, terminal ileum and vas deferens was estimated from the decline in tissue content of the amine following inhibition of its synthesis with alpha-methyl-p-tyrosine. Turnover was found to be increased in all three tissues. 4. The involvement of the polyol pathway in the above changes was investigated by examining the effects of continuous treatment with an aldose reductase inhibitor, Statil (ICI 128436) or dietary myo-inositol supplementation. Either treatment was found to prevent or reduce the increases in tissue noradrenaline and in its turnover. Myo-inositol treatment also partially prevented the rise in adrenal adrenaline. 5. It is concluded that the elevation of tissue catecholamines and of noradrenaline turnover by diabetes was related to myo-inositol depletion secondary to excessive sorbitol synthesis. Possible mechanisms for the observed increase in noradrenaline turnover could involve Na+, K+-ATPase depression.
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PMID:Tissue noradrenaline and the polyol pathway in experimentally diabetic rats. 250 23

The effect on ovulation of intraventricular infusions of noradrenaline, adrenaline and various pharmacological agents acting on the adrenergic receptor subtypes were investigated in cyclic female rats on the day of pro-oestrus. The inhibitory effects on ovulation of the different infusions were monitored by administering the drugs before 11.00 h (several hours before the critical period for the ovulatory LH surge). In experiments designed to show how the drugs under investigation might stimulate ovulation, pentobarbitone sodium (35 mg/kg) was given at 14.30 h; this anaesthetic inhibits ovulation and its effects can be overcome by substances that advance the preovulatory LH surge. Noradrenaline (an alpha-agonist) stimulated ovulation when administered on the morning of pro-oestrus to rats injected with pentobarbitone early in the afternoon of the same day. Phenoxybenzamine and phentolamine (non-selective alpha-antagonists) and clonidine (a selective alpha 2-agonist) all inhibited ovulation when infused on the morning of pro-oestrus. Yohimbine (a moderately selective alpha 2-antagonist) neither stimulated nor inhibited ovulation. Both isoprenaline (a non-selective beta-agonist) and fenoterol (a selective beta 2-agonist) stimulated ovulation in pentobarbitone-treated rats when administered on the morning of pro-oestrus and fenoterol was also able to overcome the pentobarbitone block when infused later in the afternoon. Propranolol (a non-selective beta-antagonist) and metoprolol (a selective beta 1-antagonist) were stimulatory only when administered in the afternoon. Adrenaline (both an alpha- and beta-agonist), prenalterol (a selective beta 1-agonist), atenolol (a selective beta 1-antagonist) and ICI 118,551 (a selective beta 2-antagonist) neither stimulated nor inhibited ovulation.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Evidence for a stimulatory beta-adrenergic component in the release of the ovulatory LH surge in pro-oestrous rats. 286 15

Radioligand binding studies have demonstrated convincingly the coexistence of beta 1 and beta 2 adrenoceptors in the human heart. Both subtypes are involved in the increase in tissue levels of cyclic adenosine monophosphate in isolated, electrically driven, human right atria and in the activation of adenylate cyclase in human cardiac membrane preparations. In isolated, electrically driven strips of human right atria, isoproterenol increased contractile force through stimulation of both beta 1 and beta 2 adrenoceptors, while the selective beta 2-adrenoceptor agonist, procaterol, caused its positive inotropic effect predominantly through beta 2-adrenoceptor stimulation. Norepinephrine, however, increased contractile force solely via beta 1-adrenoceptor stimulation. In this preparation, dobutamine also acted as a full agonist, producing a positive inotropic effect through stimulation of both beta-adrenoceptor subtypes. Dopexamine hydrochloride, on the other hand, having an approximately 10-fold greater affinity for right atrial beta 2 than for beta 1 adrenoceptors, acted as a partial agonist (maximal positive inotropic effect: about 30% that of isoproterenol). Similar effects have been obtained in human right and left ventricular strips; thus, there can be no doubt that cardiac beta 2 adrenoceptors can contribute to the positive inotropic effects of beta-adrenoceptor agonists in the human heart. Besides mediating positive inotropic effects, right atrial beta 2 adrenoceptors may be involved in the regulation of heart rate since, in healthy volunteers, the selective beta 2-adrenoceptor antagonist, ICI 118,551, was more potent than the selective beta 1-adrenoceptor antagonist, bisoprolol, in antagonizing isoproterenol-induced tachycardia, when both antagonists were administered in doses that selectively occupied more than 90% of beta 2 and beta 1 adrenoceptors, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The functional importance of beta 1 and beta 2 adrenoceptors in the human heart. 290 Jun 1


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