An endogenous clonidine-displacing substance from bovine brain: receptor binding and hypotensive actions in the ventrolateral medulla

Meeley, Mary P.; Ernsberger, Paul; Granata, Antonio; Reis, Donald J.

doi:10.1016/0024-3205(86)90248-1

Cited by 134 publications

(62 citation statements)

References 13 publications

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“…Pharmacologic characterization by binding assays confirmed the existence of a population of imidazoline-specific binding sites that are insensitive to catecholamines in the brainstem RVLM of animals and man (2,5,6). These studies clearly demonstrated that imidazoline binding sites are distinct from α2-adrenoceptors.…”

Section: Discovery Of Imidazoline Receptorsmentioning

confidence: 68%

Imidazoline receptors in the heart: a novel target and a novel mechanism of action that involves atrial natriuretic peptides

Mukaddam‐Daher

Gutkowska

2004

Braz J Med Biol Res

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Chronic stimulation of sympathetic nervous activity contributes to the development and maintenance of hypertension, leading to left ventricular hypertrophy (LVH), arrhythmias and cardiac death. Moxonidine, an imidazoline antihypertensive compound that preferentially activates imidazoline receptors in brainstem rostroventrolateral medulla, suppresses sympathetic activation and reverses LVH. We have identified imidazoline receptors in the heart atria and ventricles, and shown that atrial I 1 -receptors are up-regulated in spontaneously hypertensive rats (SHR), and ventricular I 1 -receptors are up-regulated in hamster and human heart failure. Furthermore, cardiac I 1 -receptor binding decreased after chronic in vivo exposure to moxonidine. These studies implied that cardiac I 1 -receptors are involved in cardiovascular regulation. The presence of I 1 -receptors in the heart, the primary site of production of natriuretic peptides, atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP), cardiac hormones implicated in blood pressure control and cardioprotection, led us to propose that ANP may be involved in the actions of moxonidine. In fact, acute iv administration of moxonidine (50 to 150 µg/rat) dose-dependently decreased blood pressure, stimulated diuresis and natriuresis and increased plasma ANP and its second messenger, cGMP. Chronic SHR treatment with moxonidine (0, 60 and 120 µg kg -1 h -1 , sc for 4 weeks) dosedependently decreased blood pressure, resulted in reversal of LVH and decreased ventricular interleukin 1ß concentration after 4 weeks of treatment. These effects were associated with a further increase in already elevated ANP and BNP synthesis and release (after 1 week), and normalization by 4 weeks. In conclusion, cardiac imidazoline receptors and natriuretic peptides may be involved in the acute and chronic effects of moxonidine. Correspondence S. Mukaddam-Daher

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Section: Discovery Of Imidazoline Receptorsmentioning

confidence: 68%

Imidazoline receptors in the heart: a novel target and a novel mechanism of action that involves atrial natriuretic peptides

Mukaddam‐Daher

Gutkowska

2004

Braz J Med Biol Res

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“…The assumption that there are non-adrenergic receptors sensitive to imidazolines was based on these data. Since then, binding studies have suggested the existence of speci®c binding sites for imidazoline compounds, which are insensitive to catecholamines (Bricca et al, 1989;Meeley et al, 1986). These imidazoline binding sites (IBS) have been classi®ed in two main subtypes (Michel & Insel, 1989).…”

Section: Introductionmentioning

confidence: 99%

Respective contributions of α‐adrenergic and non‐adrenergic mechanisms in the hypotensive effect of imidazoline‐like drugs

Bruban¹,

Feldman²,

Greney³

et al. 2001

British J Pharmacology

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1 The hypotensive e ect of imidazoline-like drugs, such as clonidine, was ®rst attributed to the exclusive stimulation of central a 2 -adrenoceptors (a 2 ARs). 2 However, a body of evidence suggests that non-adrenergic mechanisms may also account for this hypotension. 3 This work aims (i) to check whether imidazoline-like drugs with no a 2 -adrenergic agonist activity may alter blood pressure (BP) and (ii) to seek a possible interaction between such a drug and an a 2 ARs agonist a-methylnoradrenaline (a-MNA). 4 We selected S23515 and S23757, two imidazoline-like drugs with negligible a nities and activities at a 2 ARs but with high a nities for non-adrenergic imidazoline binding sites (IBS). 5 S23515 decreased BP dose-dependently (727+5% maximal e ect) when administered intracisternally (i.c.) to anaesthetized rabbits. The hypotension induced by S23515 (100 mg kg 71 i.c.) was prevented by S23757 (1 mg kg 71 i.c.) and efaroxan (10 mg kg 71 i.c.), while these compounds, devoid of haemodynamic action by themselves, did not alter the hypotensive e ect of a-MNA (3 and 30 mg kg 71 i.c.). Moreover, the a 2 ARs antagonist rauwolscine (3 mg kg 71 i.c.) did not prevent the e ect of S23515. 6 Finally, whilst 3 mg kg 71 of S23515 or 0.5 mg kg 71 of a-MNA had weak hypotensive e ects, the sequential i.c. administration of these two drugs induced a marked hypotension (723+2%). 7 These results indicate that an imidazoline-like drug with no a 2 -adrenergic properties lowers BP and interacts synergistically with an a 2 ARs agonist.

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“…both in bovine and human brain (Ernsberger et al, 1987;Bricca et al, 1988;1989a). An endogenous ligand for this receptor has been partially purified (Atlas & Burnstein, 1984a,b;Meeley et al, 1986;Ernsberger et al, 1988). In fact, a partially purified brain extract contains a substance which is not a catecholamine but displaces [3H]-clonidine bound to brain membrane preparations and increases blood pressure whereas clonidine itself reduces it (Atlas & Burstein, 1984a,b;Bousquet et al, 1986).…”

Section: Introductionmentioning

confidence: 99%

Evidence for the involvement of imidazoline receptors in the central hypotensive effect of rilmenidine in the rabbit

Feldman

Tibiriçá

Bricca

et al. 1990

British J Pharmacology

104

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1 Rilmenidine has recently been introduced as a new centrally-acting antihypertensive agent. We examined its cardiovascular effects after intracerebral injection to anaesthetized rabbits. Cumulative doses of rilmenidine injected intracisternally (1 to 300pgkg-1) led to dose-dependent decreases in arterial blood pressure and heart rate. The effective doses of rilmenidine were lower when injected centrally than when injected intravenously. 2 Pretreatment with the same dose of yohimbine or idazoxan shifted the rilmenidine dose-response curves for its hypotensive and bradycardic effects to the right. Idazoxan, which has an imidazoline structure, proved to be a more active antagonist than yohimbine of rilmenidine centrally-mediated cardiovascular effects. 3 The dose-response curve for the central hypotensive effect of rilmenidine was also shifted to the right after pretreatment with a bovine brain extract. This extract contains the endogenous ligand of the imidazoline-preferring receptors which is not a catecholamine. 4 Rilmenidine, like clonidine, proved to be active when micro-injected into the rabbit nucleus reticularis lateralis region. 5In conclusion, rilmenidine exhibited in the rabbit a central hypotensive effect which originated in the same area as where clonidine acts. Specific imidazoline-preferring receptors appear to be involved in this hypotensive effect.

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An endogenous clonidine-displacing substance from bovine brain: receptor binding and hypotensive actions in the ventrolateral medulla

Cited by 134 publications

References 13 publications

Imidazoline receptors in the heart: a novel target and a novel mechanism of action that involves atrial natriuretic peptides

Imidazoline receptors in the heart: a novel target and a novel mechanism of action that involves atrial natriuretic peptides

Respective contributions of α‐adrenergic and non‐adrenergic mechanisms in the hypotensive effect of imidazoline‐like drugs

Evidence for the involvement of imidazoline receptors in the central hypotensive effect of rilmenidine in the rabbit

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