Agmatine recognizes ?2-adrenoceptor binding sites but neither activates nor inhibits ?2-adrenoceptors

Pinthong, Darawan; Ik, Wright; Hanmer, C; Millns, Paul; Mason, Rob; Da, Kendall; Vg, Wilson

doi:10.1007/bf00169058

Cited by 79 publications

(47 citation statements)

References 3 publications

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“…Growing body of evidence supports the involvement of a 2 -adrenoceptors in mediating the actions of agmatine. Like clonidine, agmatine has been shown to bind to a 2 -adrenoceptors (Pinthong et al, 1995). Agmatine alters the firing rate of locus ceruleus neurons in vivo (Pineda et al, 1996;Ruiz-Durantez et al, 2002) and induces a 2 adrenoceptors-dependent antinociception (Onal and Soykan, 2001).…”

Section: Discussionmentioning

confidence: 99%

Agmatine Potentiates Morphine-Induced Conditioned Place Preference in Mice: Modulation by Alpha(2)-Adrenoceptors

Tahsili-Fahadan

Yahyavi-Firouz-Abadi

Khoshnoodi

et al. 2005

Neuropsychopharmacol

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The effects of agmatine, an endogenous polyamine metabolite formed by decarboxylation of L-arginine, and its combination with morphine on conditioned place preference (CPP) has been investigated in male mice. Our data show that subcutaneous administration of morphine (1-7.5 mg/kg) significantly increases the time spent in the drug-paired compartment in a dose-dependent manner. Intraperitoneal administration of agmatine (1-40 mg/kg) alone does not induce either CPP or conditioned place aversion, while combination of agmatine and subeffective doses of morphine leads to potent rewarding effects. Lower doses of morphine (0.1, 0.05, and 0.01 mg/kg) are able to induce CPP in mice pretreated with agmatine 1, 5, and 10 mg/kg, respectively. Concomitant intraperitoneal administration of UK 14 304 (0.5 mg/kg), a highly selective a 2 -agonist, with per se noneffective dose of morphine (0.5 mg/kg) and also its combination with noneffective doses of agmatine (1 mg/kg) plus morphine (0.05 mg/kg) produces significant CPP. UK 14 304 (0.05, 0.5 mg/kg) alone, or in combination with agmatine (1, 5 mg/kg) have had no effect. We have further investigated the possible involvement of the a 2 -adrenoceptors in the potentiating effect of agmatine on morphine-induced place preference. Selective a 2 -antagonists, yohimbine (0.005 mg/kg) and RX821002 (0.1, 0.5 mg/kg), block the CPP induced by concomitant administration of agmatine (5 mg/kg) and morphine (0.05 mg/kg). Yohimbine (0.001-0.05 mg/kg) or RX821002 (0.05-0.5 mg/kg) alone or in combination with morphine (0.05 mg/kg) or agmatine (5 mg/kg) fail to show any significant place preference or aversion. Our results indicate that pretreatment of animals with agmatine enhances the rewarding properties of morphine via a mechanism which may involve a 2 -adrenergic receptors.

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Section: Discussionmentioning

confidence: 99%

Agmatine Potentiates Morphine-Induced Conditioned Place Preference in Mice: Modulation by Alpha(2)-Adrenoceptors

Tahsili-Fahadan

Yahyavi-Firouz-Abadi

Khoshnoodi

et al. 2005

Neuropsychopharmacol

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“…Some conflicting studies on the role of ␣ 2-adrenergic receptors in agmatine effects have been published. Although agmatine can bind to ␣ 2 -adrenergic receptors, it does not activate them (Pinthong et al 1995a). Agmatine has no activity at ␣ 2 -adrenoceptors modulating the firing rate of locus coeruleus neurones (Pineda et al 1996) and, thus, agmatine alone is unlikely to account for all of the biological activity of clonidine-displacing substance (Piletz et al 1995; Pinthong et al 1995 a,b).…”

Section: Discussionmentioning

confidence: 99%

Agmatine Potentiates the Analgesic Effect of Morphine by an α2-Adrenoceptor-Mediated Mechanism in Mice

Yeşilyurt

Uzbay

2001

Neuropsychopharmacology

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The effects of agmatine, which is an endogenous polyamine metabolite formed by decarboxylation of L-arginine, and a combination of agmatine and morphine on tail-flick test have been investigated in mice. Adult maleSwiss-Webster mice were used in the study. Agmatine (10, 20 and 40 mg/kg) Agmatine is a cationic amine formed by decarboxylation of arginine by the enzyme arginine decarboxylase (Tabor and Tabor 1984). It is a biological active substance (Lortie et al. 1996) and binds with high affinity to both imidazoline and ␣ 2 -adrenergic receptors of all subclasses (Li et al. 1994;Piletz et al. 1995;Regunathan and Reis 1996;Reis and Regunathan 1998a). Recently, it has been suggested that agmatine meets many criteria for a neurotransmitter in brain. It is synthesised, stored, and released in brain; is contained in neurones and axon terminals; interacts with cell-specific receptors; and elicits biological actions within the central nervous system (Reis and Regunathan 1998a,b). Thus, results of some recent studies indicate the modulatory effects of agmatine in central nervous system. For example, agmatine selectively inhibits nitric oxide synthase (Galea et al. 1996), an enzyme converting L-arginine to nitric oxide, and the NMDA subclass of glutamate receptor channels (Yang and Reis 1999) in rat brain. Several reports indicated that an important role of NMDA receptors and nitric oxide in development of the opioid (Trujillo and Akil 1991;Adams et al. 1993;Thorat et al. 1994;Vaupel et al. 1997) et al. 2000). The drugs that have selective agonistic activity on imidazoline/ ␣ 2 -adrenergic receptors such as clonidine, xylazine, and moxonidine produce antinociceptive responses in rodents (Paalzow 1974;Browning et al. 1982;Ossipov et al. 1989;Fairbanks et al. 2000). The role of adrenoceptors, particularly the ␣ 2 subtype, in the potentiation of opioid-induced analgesia is also well known (Wigdor and Wilcox 1987;Dambisya et al. 1991). In the light of these reports, it would be expected that agmatine, another agent binding imidazoline/ ␣ 2 -receptors, should also have antinociceptive activity. Thus, some recent studies indicate modulatory effects of agmatine on opioid analgesia in mice (Kolesnikov et al. 1996;Fairbanks and Wilcox 1997) and rats (Horváth et al. 1999). It was reported that intrathecal administration of agmatine potentiated morphine-induced ␦ -opioid receptor-mediated analgesia ninefold without affecting pain thresholds and chronic administration prevented 1 -opioid receptor-mediated tolerance in mice (Kolesnikov et al. 1996;Bradley and Headley 1997). However, the mechanisms of these effects remain to be fully understood. It is not certain whether these effects are mediated by ␣ 2 -adrenergic or imidazoline receptors. On the other hand, there are limited studies investigating the antinociceptive effect of peripheral agmatine administration in rodents.The main objective of the present study was to investigate the possible effects of agmatine and an agmatinemorphine combination on nociception by using the tai...

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“…Agmatine has been suggested to be an endogenous ligand for imidazoline receptors on the basis of in-vitro experiments [45,46]. However, agmatine increases blood pressure when it is administered centrally, via the cisterna magna or by micro-injection.…”

Section: Central Imidazoline Receptors and Antihypertensives Van Zwiementioning

confidence: 99%

Central imidazoline (I1) receptors as targets of centrally acting antihypertensives

Zwieten

1997

Journal of Hypertension

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Agmatine recognizes ?2-adrenoceptor binding sites but neither activates nor inhibits ?2-adrenoceptors

Cited by 79 publications

References 3 publications

Agmatine Potentiates Morphine-Induced Conditioned Place Preference in Mice: Modulation by Alpha(2)-Adrenoceptors

Agmatine Potentiates Morphine-Induced Conditioned Place Preference in Mice: Modulation by Alpha(2)-Adrenoceptors

Agmatine Potentiates the Analgesic Effect of Morphine by an α2-Adrenoceptor-Mediated Mechanism in Mice

Central imidazoline (I1) receptors as targets of centrally acting antihypertensives

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