Vasodilatation elicited by 5-HT1A receptor agonists in constant-pressore-perfused rat kidney is mediated by blockade of α1A-adrenoceptors

Eltze, Manfrid; Boer, Rainer; Sanders, Karl H.; Kolassa, Norbert

doi:10.1016/0014-2999(91)90250-t

Cited by 70 publications

(73 citation statements)

References 27 publications

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“…Although sen- 1-18, 20-27 1, 2, 5, 7, 9, 12-16, 18, 20-23, 26, 27 1-3, 5, 7, 9, 11, 15, 16, 22, 24, 26, 27 5, 6, 11, 12, 14, 17, 19, 27 5, 11 4, 5, 7, 10-12, 14, 18-20, 22, 24-27 7, 9, 14, 24 2, 15, 16, 20 9, 17, 25, 26 Morrow & Creese, 1986;(3) Honda et al, 1987;(4) Gross et al, 1988;(5) Boer et al, 1989;(6) Hanft & Gross, 1989a; (7) Hanft & Gross, 1989b;(8) Hanft et al, 1989;(9) Michel et al, 1989;(10) (11) Michel et al, 1990;(12) Eltze et al, 1991;(13) Feng et al, 1991;(14) Klijn et al, 1991;(15) Oshita et al, 1991;Tsuchihashi et al, 1991;(17) Eltze & Boer, 1992;(18) Hiramatsu et al, 1992;(19) Jackson et al, 1992;(20) Muramatsu, 1992;(21) Ohmura et al, 1992;(22) Yazawa et al, 1992;(23) Ivorra et al, 1993;(24) Michel et al, 1993a;(25) Schwietert et al, 1993;(26) Sleight et al, 1993;(27) Kidney (pKB or pA2) Figure 8 Correlations of antagonist affinity estimates (pA2 values) at az-adrenoceptors in isolated perfused kidney of rat and antagonist affinity estimates (pK, values) in cloned (a) MIB-adrenoceptors, (b) otc-adrenoceptors and (c) alD-adrenoceptors: (1) sitivity to nitrendipine does not provide insight into the identity of the receptor, it is nevertheless an important finding as it allows pharmacological 'isolation' of the cladrenoceptor at which 5-methyl-urapidil exerts high affinity and, therefore, characterization and classification of the site. For this reason, agonists and antagonists (tested subsequently to using 5-methyl-urapidil) were studied in the presence of nitrendipine (see Table 1).…”

Section: Discussionmentioning

confidence: 99%

Functional evidence equating the pharmacologically‐defined α_1A‐ and cloned α_1C‐adrenoceptor: studies in the isolated perfused kidney of rat

Blue¹,

Bonhaus²,

Ford³

et al. 1995

British J Pharmacology

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1 The present study characterizes and classifies ax-adrenoceptor-mediated vasoconstriction in the isolated perfused kidney of rat using quantitative receptor pharmacology and compares the results to radioligand binding studies (made in cloned al-adrenoceptor subtypes, native aIA-adrenoceptors in submaxillary gland of rat, and MIA-adrenoceptors in several other tissues of rat).2 Concentration-effect curves to noradrenaline in the presence of 5-methyl-urapidil were biphasic, indicating al-adrenoceptor heterogeneity. The al-adrenoceptor subtype mediating the first phase (low affinity for 5-methyl-urapidil) could not be 'isolated' for detailed pharmacological characterization but was defined by a sensitivity to inhibition by chloroethylclonidine and an inability of methoxamine to activate the site. Additionally, vasoconstriction mediated by this aI-adrenoceptor subtype or subtypes was abolished by nitrendipine (1 JLM), thereby allowing characterization of the second, high affinity site for 5-methyl-urapidil.3 The following antagonists interacted competitively with noradrenaline at the al-adrenoceptor for which 5-methyl-urapidil exhibits high affinity (pKB value): WB 4101 (10.3)>prazosin (9.5)--HV 723 (9.3) -5-methyl-urapidil (9.2)>phentolamine (8.6)>spiperone (pA2 = 8.1)toxymetazoline (7.9). In contrast, insurmountable antagonism was seen with S(+)-and R(-)-niguldipine, the S(+ )-isomer being approximately 30 fold more potent than the R(-)-isomer. Receptor protection experiments indicated that S(+)-niguldipine interacted directly with a,-adrenoceptors. Dehydroniguldipine acted as a competitive antagonist (pKB =9.0). Thus, the results with antagonists define the aI-adrenoceptor as an cXIA-adrenoceptor. 4 An agonist 'fingerprint' was constructed in the presence of nitrendipine to define further the aIA-adrenoceptor. The following order and relativity of agonist potency was obtained: cirazoline (1)t adrenaline (2)>noradrenaline (5) 6 The present study demonstrates that the MlA-adrenoceptor is the predominant a-adrenoceptor subtype mediating vasoconstrictor responses to exogenously administered noradrenaline in the isolated perfused kidney of rat. More importantly, OIA-adrenoceptors mediating vasoconstrictor responses to noradrenaline exhibited a pharmacological equivalency to the cloned bovine xic-adrenoceptor. Thus, definitive functional pharmacological data are provided for equating the two receptors and support results derived recently from molecular and radioligand binding studies.

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Section: Discussionmentioning

confidence: 99%

Functional evidence equating the pharmacologically‐defined α_1A‐ and cloned α_1C‐adrenoceptor: studies in the isolated perfused kidney of rat

Blue¹,

Bonhaus²,

Ford³

et al. 1995

British J Pharmacology

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“…The experiments were performed on kidneys taken frorn normotensive rats (Sprague-Dawley, male, 400-450 g, Wiga, Sulzfeld, Germany ), similarly to the method described previously (Eltze et al, 1991). Briefly, after the aorta adjacent to the left renal artery bad been cannulated and the abdominal vena cava cut, the kidney was removed and perfused at a constant pressure.…”

Section: Rat Isolated Perfused Kidneymentioning

confidence: 99%

Characterization of muscarinic receptorsmediating vasodilation in rat perfused kidney

Eltze

Ullrich

Mutschler

et al. 1993

European Journal of Pharmacology

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The muscarinic receptor mediating vasodilation of resistance vesse]s in the rat iso]ated, constant-pressure perfused kidney vasodilation disappeared after destruction of the endothelium with detergent. Highly significant correlations of agonist potencies for vasodilation were found between rat kidney and guinea-pig ileum submucosal arterioles as weH as agonist potencies at smooth muscle muscarinic M 3 receptors of the guinea-pig ileum. The rank order of antagonist potencies (4-diphenylacetoxy-Nmethylpiperidine methiodide (4-DAMP) > (R)-hexahydro-difenidol -hexahydro-sila-difenidol > pirenzepine -p-fluorohexahydro-sila-difenidol-himbacine-AF-DX 384-AQ-RA 741 > (S)-hexahydro-difenidol) to attenuate vasodilation to APE in rat kidney, correlated significantly with affinities at M 3 receptors in submucosal arterioles and in smooth muscle of the guinea-pig ileum, but differed from those at M 1 and M 2 receptors in rabbit vas deferens. The agonist and antagonist potencies suggest that vasodilation elicited by muscarinic stimuli in endothelium-intact rat renal vasculature is mediated by functional muscarinic M 3 rcceptors.

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“…The affinities obtained in our study with a range of a,-adrenoceptor antagonists against NA-induced contractions of rat vas deferens are consistent with other reported values (Han et al, 1987;Eltze & Boer, 1992;Couldwell et al, 1993) which suggest the contractile element of this tissue in response to exogenous NA to be predominantly mediated via MIA-adrenoceptors. Other studies have been able to demonstrate an excellent correlation between the affinity of antagonists against NA-induced contractions of rat vas deferens and the affinity for MIA sites in rat cortex labelled by [3H]-prazosin (Eltze et al, 1991;Eltze & Boer, 1992). This is in agreement with our findings in relation to the nature of the cloned rat OlA/D-adrenoceptor which we have found to be characteristic of this subtype in cortex and vas deferens, consistent with Northern analysis of the distribution of this receptor using a rat CIA cDNA probe (Lomasney et al, 1991).…”

Section: Oca-adrenoceptors In Rat Cortex and Vas Deferens 1007mentioning

confidence: 99%

Pharmacological properties of the cloned α_1A/D‐adrenoceptor subtype are consistent with the α_1A‐adrenoceptor characterized in rat cerebral cortex and vas deferens

Kenny

Naylor

Greengrass

et al. 1994

British J Pharmacology

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XIA/D-receptors were consistent with a1A affinities determined with chlorethylclonidine-treated rat cortical membranes. Affinities at cloned XIB-receptors were consistent with m affinities determined with rat liver membranes.6 Using the epididymal rat vas deferens as a functional measure of aIA affinity, prazosin (pA2 9.23 ± 0.28), WB 4101 (pA2 9.58 0.12), phentolamine (pKB 7.90 ± 0.16), benoxathian (pKB 9.21 ± 0.21) and 5-methyl-urapadil (pKB 8.51 0.16) were potent antagonists of noradrenaline-induced contractions.7 At present, evidence from cloning studies suggests the existence of at least three a,-adrenoceptor subtypes. In contrast to the recent proposal for al-adrenoceptor classification, the pharmacology of the cloned a1A/D (or alD)-adrenoceptor is more consistent with that of an XIA-adrenoceptor characterized in rat cerebral cortex and vas deferens.

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Vasodilatation elicited by 5-HT1A receptor agonists in constant-pressore-perfused rat kidney is mediated by blockade of α1A-adrenoceptors

Cited by 70 publications

References 27 publications

Functional evidence equating the pharmacologically‐defined α_1A‐ and cloned α_1C‐adrenoceptor: studies in the isolated perfused kidney of rat

Functional evidence equating the pharmacologically‐defined α_1A‐ and cloned α_1C‐adrenoceptor: studies in the isolated perfused kidney of rat

Characterization of muscarinic receptorsmediating vasodilation in rat perfused kidney

Pharmacological properties of the cloned α_1A/D‐adrenoceptor subtype are consistent with the α_1A‐adrenoceptor characterized in rat cerebral cortex and vas deferens

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Vasodilatation elicited by 5-HT1A receptor agonists in constant-pressore-perfused rat kidney is mediated by blockade of α1A-adrenoceptors

Cited by 70 publications

References 27 publications

Functional evidence equating the pharmacologically‐defined α1A‐ and cloned α1C‐adrenoceptor: studies in the isolated perfused kidney of rat

Functional evidence equating the pharmacologically‐defined α1A‐ and cloned α1C‐adrenoceptor: studies in the isolated perfused kidney of rat

Characterization of muscarinic receptorsmediating vasodilation in rat perfused kidney

Pharmacological properties of the cloned α1A/D‐adrenoceptor subtype are consistent with the α1A‐adrenoceptor characterized in rat cerebral cortex and vas deferens

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Functional evidence equating the pharmacologically‐defined α_1A‐ and cloned α_1C‐adrenoceptor: studies in the isolated perfused kidney of rat

Functional evidence equating the pharmacologically‐defined α_1A‐ and cloned α_1C‐adrenoceptor: studies in the isolated perfused kidney of rat

Pharmacological properties of the cloned α_1A/D‐adrenoceptor subtype are consistent with the α_1A‐adrenoceptor characterized in rat cerebral cortex and vas deferens