Investigations of prejunctional α2-adrenoceptors in rat atrium, vas deferens and submandibular gland

Smith, Karen; Connaughton, Sonia; Docherty, James R.

doi:10.1016/0014-2999(92)90536-d

Cited by 36 publications

(29 citation statements)

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“…Macmillan Press Ltd, 1992 atrial receptors was confirmed and the submaxillary receptors, like those of the vas deferens, were classified as a2A. Our study suggests a reinterpretation of some findings of Smith et al (1992).…”

Section: Introductionmentioning

confidence: 61%

“…d Michel et al (1989). Previous c2-autoreceptor characterizations Smith et al (1992) have recently classified the a2-autoreceptors of rat submaxillary gland and rat vas deferens as a2A and those of rat atrium as a2B. They based their conclusion on a comparison with their own binding data for a2A and a2B sites and did not attempt a classification in terms of a2C or a2D.…”

Section: Properties Of the A2-autoreceptorsmentioning

confidence: 99%

“…The difference is real: the same similarities and differences were detected in two independent assessments of autoreceptor properties ( Figure 3a versus Figure 3b). On the other hand, we would like to suggest that the results of Smith et al (1992) (Connaughton & Docherty, 1989;Smith et al, 1992) with the binding sites listed in our & Docherty, 1989).…”

Section: Properties Of the A2-autoreceptorsmentioning

confidence: 99%

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Pharmacological characterization of presynaptic α₂‐autoreceptors in rat submaxillary gland and heart atrium

Limberger

Trendelenburg

Starke

1992

British J Pharmacology

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1 The pharmacological properties of presynaptic M2-autoreceptors were studied in rat isolated submaxillary glands and atria. Tissue pieces were preincubated with [3H]-noradrenaline, then superfused with medium containing desipramine, and stimulated electrically. In one series of experiments, pEC30 values of 12 x-adrenoceptor antagonists were determined, i.e., negative logarithms of concentrations that increased the electrically evoked overflow of tritium by 30%. In another series, pKD values of 9 aadrenoceptor antagonists against the release-inhibiting effect of 5-bromo-6-(2-imidazolin-2-ylamino)-quinoxaline (UK 14304), and of 3 antagonists against the release-inhibiting effect of methoxamine, were determined.2 In submaxillary glands, the pEC30 values of the antagonists correlated well with their pKD values against UK 14304 (r = 0.93). The same was true for atria (r = 0.92).3 In submaxillary glands, the pKD values of 3 antagonists against UK14304 were very similar to their pKD values against methoxamine, with a maximal difference of 0.4. The same was true for atria where the maximal difference was 0.3. 4 The pEC30 values obtained in submaxillary glands correlated significantly with those obtained in atria (r = 0.81). The same was true for the pKD values (r = 0.79). However, the pEC30 and pKD values also indicated consistent differences between the two tissues. 5 It is concluded that the sites of action of the imidazoline UK 14304 (x2-selective), the phenylethylamine noradrenaline, and the phenylethylamine methoxamine (a,-selective) are exclusively a2-adrenoceptors. There is no indication for presynaptic a,-adrenoceptors or for an effect of UK 14304 mediated by presynaptic imidazoline receptors. The 02-autoreceptor population in the submaxillary gland differs from that in the atrium. 6 Comparison with studies from the literature indicates that the submaxillary autoreceptors are closely similar to the a2D radioligand binding site found in the bovine pineal gland and probably the rat submaxillary gland. The atrial autoreceptors also conform best to this site, but the agreement is more limited; the atrial autoreceptors may represent a type related to, but distinct from, the a2D site, or a mixture of different types.

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Section: Introductionmentioning

confidence: 61%

Section: Properties Of the A2-autoreceptorsmentioning

confidence: 99%

Section: Properties Of the A2-autoreceptorsmentioning

confidence: 99%

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Pharmacological characterization of presynaptic α₂‐autoreceptors in rat submaxillary gland and heart atrium

Limberger

Trendelenburg

Starke

1992

British J Pharmacology

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“…However, a slightly lower pA2 value (9.3) with a slope less than unity (0.7) was obtained in the rat vas deferens. The reason for this is unknown, but it could be due to the presence of a mixed population of subtypes of prejunctional M2-adrenoceptors, as has been suggested recently for this tissue (Harsing & Vizi, 1992;Smith et al, 1992).…”

Section: Mydriasis Studiesmentioning

confidence: 99%

“…The particular subtypes ofa2-adrenoceptors which mediate responses to M2-adrenoceptor agonists in the guinea-pig ileum, rat vas deferens and dog saphenous vein are as yet unclear, and species differences may exist (Ruffolo et al, 1991;Limberger et al, 1992;Smith et al, 1992). RS-15385-197 exhibited no selectivity between prejunctional (pA2 in guinea-pig ileum 9.7) and postjunctional (pA2 in dog saphenous vein 10.0) M2-adrenoceptors in vitro.…”

Section: Mydriasis Studiesmentioning

confidence: 99%

The pharmacology of RS‐15385‐197, a potent and selective α₂‐adrenoceptor antagonist

Brown¹,

MacKinnon²,

Redfern³

et al. 1993

British J Pharmacology

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1 RS-15385-197 ((8aR, 12aS, 13aS)-5,8,8a,9,10,11,12,12a,13,13a-decahydro-3-methoxy-12-(methylsulphonyl RS-15385-197. 5 RS-15385-197 was non-selective for the a2A-and M2B-adrenoceptor subtypes in that the pKi for the aX2A-adrenoceptor in human platelets was 9.90 and the pKi for the x2B-adrenoceptor in rat neonate lung was 9.70. However, RS-15385-197 showed lower affinity for the m2-adrenoceptor subtype in hamster adipocytes (pKi 8.38). 6 In anaesthetized rats, RS-15385-197 was a potent antagonist of the mydriasis response induced by UK-14,304 or clonidine (AD50 5 and 7 pg kg-', i.v., respectively; 96 1g kg-', p.o.) and of induced pressor responses in pithed rats (ADI0 7 pg kg-', i.v.); the compound therefore is both centrally and orally active. Even at a high dose (10mg kg-', i.v.), RS-15385-197 did not antagonize pressor responses to cirazoline in pithed rats, indicating that the selectivity for a2 vs. xl-adrenoceptors was maintained in vivo.8 RS-15385-197 is therefore a very potent, selective, competitive m2-adrenoceptor antagonist, both in vitro and in vivo, is orally active and readily penetrates the brain. It will thus be a powerful pharmacological tool for exploring the various physiological roles of aX2-adrenoceptors.

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α‐Adrenoceptor Assays

Hancock

1998

CP Pharmacology

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Important in numerous physiological processes, α-adrenoceptors were among the first receptors identified by use of pharmacological techniques. These receptors are pivotal in controlling cardiovascular function both within the central nervous system and at the periphery, and play major roles in other autonomic functions. In addition, α-adrenoceptors influence the release of other neurotransmitters from synaptic terminals in both the central and peripheral nervous systems. The influence of α-adrenoceptors over autonomic and central nervous system function is thus far reaching. BASIC PROTOCOL 1 EVALUATION OF α 1A -ADRENOCEPTORS IN ISOLATED VAS DEFERENSThis protocol describes the steps required to isolate the rat vas deferens, equilibrate the tissue, and characterize baseline responses to adrenergic compounds. These procedures facilitate study of the pharmacology of responses, either to establish the pharmacological characteristics of the receptors within the tissue or to determine the pharmacological effects of an unknown compound. The latter goal is best achieved using parallel assays for other adrenoceptor subtypes in tissue selectively enriched for those receptors.As with other models employing isolated animal tissues, the tissue must be harvested expeditiously, with oxygenation maintained during preparation and throughout the course of the experiment. Buffered physiological salt solutions continuously bubbled with carbogen (95%O 2 /5% CO 2 ) maintain the correct acid/base balance of the buffer and the oxygen content of the tissue. Aeration also thoroughly mixes test agents in the tissue bath, so that the equilibration time between drug addition and exposure at the receptor sites is rapid.

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Investigations of prejunctional α2-adrenoceptors in rat atrium, vas deferens and submandibular gland

Cited by 36 publications

References 10 publications

Pharmacological characterization of presynaptic α₂‐autoreceptors in rat submaxillary gland and heart atrium

Pharmacological characterization of presynaptic α₂‐autoreceptors in rat submaxillary gland and heart atrium

The pharmacology of RS‐15385‐197, a potent and selective α₂‐adrenoceptor antagonist

α‐Adrenoceptor Assays

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Investigations of prejunctional α2-adrenoceptors in rat atrium, vas deferens and submandibular gland

Cited by 36 publications

References 10 publications

Pharmacological characterization of presynaptic α2‐autoreceptors in rat submaxillary gland and heart atrium

Pharmacological characterization of presynaptic α2‐autoreceptors in rat submaxillary gland and heart atrium

The pharmacology of RS‐15385‐197, a potent and selective α2‐adrenoceptor antagonist

α‐Adrenoceptor Assays

Contact Info

Product

Resources

About

Pharmacological characterization of presynaptic α₂‐autoreceptors in rat submaxillary gland and heart atrium

Pharmacological characterization of presynaptic α₂‐autoreceptors in rat submaxillary gland and heart atrium

The pharmacology of RS‐15385‐197, a potent and selective α₂‐adrenoceptor antagonist