A role for mast cells in adenosine A<sup>3</sup> receptor‐mediated hypotension in the rat

Hannon, Jason P.; Pfannkuche, Hans-Juergen; Fozard, John R.

doi:10.1111/j.1476-5381.1995.tb15902.x

Cited by 125 publications

(117 citation statements)

References 25 publications

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“…In the presence of the histamine antagonist diphenhydramine, the 8-pSPT-resistant component of the response to APNEA was not modi®ed. These data are not in agreement with those reported for experiments in anaesthetized rats, where the hypotensive xanthine-resistant response to APNEA was well correlated with histamine plasma increase and blocked by the A 3 antagonist BW-A522, and by the mast cell stabilizer sodium chromoglycate (Fozard & Hannon, 1994;Patel et al, 1994;Hannon et al, 1995). It should be underlined that the role observed for A 3 receptors on rat mast cells (Fozard et al, 1996) is not con®rmed in other animals such as dogs and humans (Auchampach et al, 1997;Feoktistov & Biaggioni, 1997) and, as far as the guinea-pig is concerned, there is no report about a clear characterization of adenosinic receptor subtypes on mast cells.…”

Section: Discussioncontrasting

confidence: 97%

“…A role for A 3 receptors at the cardiovascular level has also been suggested by di erent authors: a hypotensive e ect of adenosine analogues in the presence of both A 1 and A 2 receptor blockade has been reported in anaesthetized and pithed rats, which was antagonized by the A 3 antagonist BW-A522 (Fozard & Hannon, 1994) and was linked to mediator release from mast cells (Hannon et al, 1995); in contrast, a vasoconstrictor response to adenosine via A 3 -mediated mast cell degranulation has been described in in vivo hamster (Shepherd et al, 1996). At the cardiac level, A 3 receptor stimulants, administered prior to and during an ischaemic episode, have shown a protective action on heart cells in human and other animals (Strickler et al, 1996;Stambaugh et al, 1997;Tracey et al, 1997;Carr et al, 1997).…”

Section: Introductionmentioning

confidence: 82%

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Adenosine‐mediated hypotension in in vivo guinea‐pig: receptors involved and role of NO

Nieri¹,

Martinotti²,

Calderone³

et al. 2001

British J Pharmacology

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1 Adenosine produced a biphasic lowering of the mean BP with a drastic bradycardic e ect at the highest doses. The ®rst phase hypotensive response was signi®cantly reduced by the nitric oxide (NO) synthase inhibitor L-NAME. 2 The A 2a /A 2b agonist NECA produced hypotensive and bradycardic responses similar to those elicited by adenosine, which were not signi®cantly modi®ed by the A 2b antagonist enprofylline. 3 The A 2a agonist CGS 21680 did not signi®cantly in¯uence basal HR while induced a hypotensive response antagonized by the A 2a selective antagonist ZM 241385, and reduced by both L-NAME and the guanylate cyclase inhibitor methylene blue. 4 The A 1 agonist R-PIA showed a dose-dependent decrease in BP with a drastic decrease in HR at the highest doses. The A 1 selective antagonist DPCPX signi®cantly reduced the bradycardic activity and also the hypotensive responses obtained with the lowest doses while it increased those obtained with the highest ones. 5 The A 1 /A 3 agonist APNEA, in the presence of the xanthinic non-selective antagonist 8-pSPT, maintained a signi®cant hypotensive, but not bradycardic, activity, not abolished by the histamine antagonist diphenhydramine. 6 The selective A 3 agonist IB-MECA revealed a weak hypotensive and bradycardic e ect, but only at the highest doses. 7 In conclusion, in the systemic cardiovascular response to adenosine two major components may be relevant: an A 2a -and NO-mediated hypotension, and a bradycardic e ect with a consequent hypotension, via atypical A 1 receptors. Finally, an 8-pSPT-resistant hypotensive response not attributable to A 3 receptor-stimulation or to release of histamine by mastocytes or other immune cells was observed. IntroductionFour classes of membrane surface adenosine receptors are described, de®ned A 1 , A 2a , A 2b and A 3 , through which the nucleoside in¯uences many functions in humans and other animals (Ralevic & Burnstock, 1998). As far as the cardiovascular system is concerned, adenosine slows heart rate (HR) and atrioventricular conduction and antagonizes the cardio-stimulatory e ects of catecholamines via cardiac A 1 receptors in di erent mammals (Belardinelli et al., 1989;Olsson & Pearson, 1990). An increase in blood pressure (BP) and HR has been described in rats and in cats via central A 1 receptors (St Lambert et al., 1994; SilvaCarvalho et al., 1993). In contrast, a dose-related decrease in BP and HR is observed after microinjection of adenosine into the caudal nucleus of tractus solitarii in the rat (Lo et al., 1998).As regards a direct e ect on blood vessels, A 1 purinoceptors mediate vasodilation in the porcine coronary artery (Merkel et al., 1992) but they are involved, on the contrary, in vasoconstrictor responses, i.e. in the rat kidney (Jackson, 1991), in guinea-pig pulmonary artery and aorta (Biaggioni et al., 1989;Stoggall & Shaw, 1990) and in hamster skin (Stojanov & Proctor, 1990;Proctor & Stojanov, 1991).Moreover, a signi®cant role of A 1 receptors in the regulation of BP also appears to be linked to a prejunction...

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Section: Discussioncontrasting

confidence: 97%

Section: Introductionmentioning

confidence: 82%

Adenosine‐mediated hypotension in in vivo guinea‐pig: receptors involved and role of NO

Nieri¹,

Martinotti²,

Calderone³

et al. 2001

British J Pharmacology

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“…Therefore, a positive L in the QSAR equation (5) suggests that there are long substituents in a specific direction. The fractional charged partial surface area (FPSA 3 ) is obtained by dividing atomic charge weighted positive surface area by the total molecular solvent-accessible surface area [24] and negative FPSA 3 values are favored on the bond axis.…”

Section: Qsar Analysismentioning

confidence: 99%

“…Density (ρ), which is defined as the ratio of molecular weight to molecular volume inside the contact surface, can be used to reflect how tightly a molecule fits into the binding site and a negative coefficient of density indicates that packed molecules are of low activity. In order to perform further analyses on the QSAR equation (5), the data set was divided into five subgroups and a linear regression was performed on each subgroup using one or two of the descriptors from the QSAR equation (5). The subgroup members, corresponding regression equations and correlation coefficients are presented in Table 5.…”

Section: Qsar Analysismentioning

confidence: 99%

“…The A 3 receptor is activated by adenosine or agonists by activating inhibitory G proteins, it inhibits the generation of cAMP by adenylate cyclase [4]. However, activation of the human A 3 receptor results in hypotension and release of inflammatory mediators from mast cells [5][6]. At present, human A 3 receptor antagonists are being investigated as potential antiinflammatory, anti-asthmatic and anti-ischemic agents [7].…”

Section: Introductionmentioning

confidence: 99%

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Triazoloquinazolines as Human A3 Adenosine Receptor Antagonists: A QSAR Study

Kim

Hong

Lee

2006

IJMS

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Abstract:Multiple linear regression analysis was performed on the quantitative structureactivity relationships (QSAR) of the triazoloquinazoline adenosine antagonists for human A 3 receptors. The data set used for the QSAR analysis encompassed the activities of 33 triazoloquinazoline derivatives and 72 physicochemical descriptors. A template molecule was derived using the known molecular structure for one of the compounds when bound to the human A 2B receptor, in which the amide bond was in a cis-conformation. All the test compounds were aligned to the template molecule. In order to identify a reasonable QSAR equation to describe the data set, we developed a multiple linear regression program that examined every possible combination of descriptors. The QSAR equation derived from this analysis indicates that the spatial and electronic effects is greater than that of hydrophobic effects in binding of the antagonists to the human A 3 receptor. It also predicts that a large sterimol length parameter is advantageous to activity, whereas large sterimol width parameters and fractional positive partial surface areas are nonadvatageous.

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Cardiovascular pharmacology of SCH 59761, a highly potent, non-selective, adenosine receptor agonist

et al. 1996

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A role for mast cells in adenosine A³ receptor‐mediated hypotension in the rat

Abstract: 1 The adenosine A3 receptor agonist, N6-2-(4-aminophenyl)ethyladenosine (APNEA) induces hypotension in the anaesthetized rat

Cited by 125 publications

References 25 publications

Adenosine‐mediated hypotension in in vivo guinea‐pig: receptors involved and role of NO

Adenosine‐mediated hypotension in in vivo guinea‐pig: receptors involved and role of NO

Triazoloquinazolines as Human A3 Adenosine Receptor Antagonists: A QSAR Study

Cardiovascular pharmacology of SCH 59761, a highly potent, non-selective, adenosine receptor agonist

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A role for mast cells in adenosine A3 receptor‐mediated hypotension in the rat

Abstract: 1 The adenosine A3 receptor agonist, N6-2-(4-aminophenyl)ethyladenosine (APNEA) induces hypotension in the anaesthetized rat

Cited by 125 publications

References 25 publications

Adenosine‐mediated hypotension in in vivo guinea‐pig: receptors involved and role of NO

Adenosine‐mediated hypotension in in vivo guinea‐pig: receptors involved and role of NO

Triazoloquinazolines as Human A3 Adenosine Receptor Antagonists: A QSAR Study

Cardiovascular pharmacology of SCH 59761, a highly potent, non-selective, adenosine receptor agonist

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A role for mast cells in adenosine A³ receptor‐mediated hypotension in the rat