No evidence for differences between pre‐ and post‐junctional α<sub>2</sub>‐adrenoceptors

Docherty, James R.; Hyland, Lisa

doi:10.1111/j.1476-5381.1985.tb08901.x

Cited by 28 publications

(9 citation statements)

References 13 publications

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“…An augmented residual constrictor response at 24'C as compared to 37°C has also been observed in the canine saphenous vein (Flavahan & Vanhoutte, 1986b) and, in addition, not only in venous preparations but also in the rat isolated mesenteric vasculature (Yamamoto et al, 1992 (Flavahan & Vanhoutte, 1986a). Another likely explanation is that sympathetic cotransmitters are inactivated more slowly at lower temperatures as has been shown for ATP in the guinea-pig vas deferens (Cunnane & Manchanda, 1988 (Janssens & Verhaeghe, 1983;Gothert et al, 1984;Docherty & Hyland, 1985b;see Starke, 1977). Electrical stimulation caused not only an overflow of tritium but also an overflow of ATP.…”

Section: Ax-adrenoceptor-mediated Constrictor Responsesmentioning

confidence: 94%

A study of ATP as a sympathetic cotransmitter in human saphenous vein

Rump

Kügelgen

1994

British J Pharmacology

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Section: Ax-adrenoceptor-mediated Constrictor Responsesmentioning

confidence: 94%

A study of ATP as a sympathetic cotransmitter in human saphenous vein

Rump

Kügelgen

1994

British J Pharmacology

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“…Results with the CX2-adrenoceptor antagonist, yohimbine, were less clear cut: yohimbine caused the response to NA to be resistant to prazosin whether or not CEC had been administered. Hence, we also investigated the actions of the a2-adrenoceptor selective agonist, xylazine (Docherty & Hyland, 1985). Xylazine contracted the aorta only in relatively high concentrations, making it difficult to carry out interaction experiments, but these contractions were not blocked by yohimbine and resistant to prazosin.…”

Section: Discussionmentioning

confidence: 99%

Investigation of the actions of chloroethylclonidine in rat aorta

O'rourke

Kearns

Docherty

1995

British J Pharmacology

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1 The interaction between chloroethylclonidine (CEC) and noradrenaline (NA) has been examined at aadrenoceptors mediating contractions of rat aorta. 2 In rat aorta, the competitive antagonist prazosin, over the concentration-range 0.01-10 gM, produced concentration-dependent shifts in the contractile potency of NA, so that there was no component of the NA contraction resistant to prazosin.3 The irreversible a,-adrenoceptor antagonists, phenoxybenzamine (PBZ) (1-10 gM) and benextramine (10 JiM) produced shifts in potency of NA and reduced the maximum response in a concentrationdependent manner. 4 The irreversible a,-adrenoceptor antagonist, CEC (100 gM), produced a non-parallel shift in the NA concentration-response curve so that low concentrations of NA produced relatively small contractions but relatively high concentrations produced further contractions, so that the maximum response was not significantly reduced.5 The combination of CEC pretreatment and subsequent prazosin (0.1 gM) produced a parallel shift in the potency of NA. However, prazosin (10 gM) failed to produce any further effect on the response to high concentrations of NA following CEC pretreatment. Hence, a component of the contraction to NA in the presence of CEC was resistant to subsequent prazosin. Likewise, this component was resistant to a combination of prazosin (10 uM) and yohimbine (10 gM).6 Receptor protection experiments were carried out in which tissues were exposed to NA (100 MM), yohimbine (10 gM) or prazosin (0.1 Mm) prior to and during exposure to CEC. Receptor protection with NA, yohimbine or prazosin (0.1 gM), followed by washout prevented the shift in potency of NA produced by CEC.7 Further experiments examined the effects of prazosin (10 gM) on responses to NA following receptor protection with NA (100 uM), yohimbine (10 gM), prazosin (10 gM), or xylazine (100 gM). In receptor protection studies with NA, subsequent prazosin (10 gM) produced a shift in response to NA following CEC which was not signficantly different from the shift produced by prazosin alone in the absence of receptor protection. In receptor protection studies with prazosin, yohimbine or xylazine, subsequent prazosin (10 gM) produced shifts in the response to NA following CEC which were significantly less than the shift produced by prazosin alone in the absence of receptor protection. 8 It is concluded that CEC has two actions in the rat aorta. Firstly, it behaves as an irreversible a,-adrenoceptor antagonist, reducing the response to low concentrations of NA (up to 10 gM). However, after exposure to CEC, concentrations of NA of 10 gM and above produced contractions resistant to prazosin. This resistant component was still present following receptor protection with a,-or a2-adrenoceptor antagonists, but absent following receptor protection with NA. Hence, the latter response may represent an irreversible agonist interaction between CEC, NA and a-adrenoceptors which cannot be affected by subsequent competitive antagonism, but which can be prevented by receptor ...

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“…Are there differences between pre-and post-junctional a2-adrenoceptors? Early studies provided no evidence for a major difference between the two anatomically different receptors (Skarby, 1984a;Docherty & Hyland, 1985), but various reports indicated significant differences between a2-adrenoceptors in different species (Alabaster & Peters, 1984;Waterfall, Rhodes & Lattimer, 1985). For example, the selective a2adrenoceptor antagonist WY 26703 was more potent at pre-junctional a2-adrenoceptors in the rat left atrium and rat vas deferens (pA2 approximately 8&3) than at post-junctional a2adrenoceptors in the rabbit saphenous vein (pA2 = 6-3), but it became apparent that it was also less potent at pre-junctional cx2-adrenoceptors in the rabbit Alabaster, Keir & Peters, 1986).…”

Section: C2-adrenoceptorsmentioning

confidence: 99%

Are there more than two types of alpha‐adrenoceptors involved in physiological responses?

Wilson¹,

Cm²,

Jc³

1991

Experimental Physiology

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The application of the four main techniques available for examining the properties of alpha‐adrenoceptors, gene coding, radioligand, biochemical and functional methods, has reinforced the earlier subclassification (alpha 1‐ and alpha 2‐subtypes). These different techniques have not yet yielded subclassifications which entirely align when the subtypes have been examined in detail, although a prime reason for this is that the different techniques have not yet all been applied to the same receptors. There is evidence available on each level to indicate that there are further subtypes within the alpha 1‐ and alpha 2‐adrenoceptors as originally defined pharmacologically, with the possible exception of functional evidence at cellular and tissue level for subtypes of alpha 2. The present extension of the subclasses to three each (A,B,C) for alpha 1 and alpha 2 does not withstand cross‐examination on every level and seems unlikely to withstand further probing. It remains true that the set of subtypes of alpha‐adrenoceptor which can be activated or blocked by drugs in functioning intact tissue preparations and which are shown in Fig. 4 has not been added to by knowledge derived from ligand binding or molecular biology. These techniques have bolstered confidence in the existing functioning categories and have enabled acceleration of drug screening programmes to find new, potent, highly selective antagonists for the known receptors. Rather than taking the categorization of receptors away from the recognition site to the larger molecule, they have reinforced its supremacy. The advantages being gained from the molecular biology of receptors lie in understanding cell signalling and, on the wider genetic scale, on the place of the receptors, among other elements of the cell, in regulation and function within the organism. From the physiologist's point of view, classical pharmacology can still be relied on as the basis for understanding the specificity of drugs which activate or block plasmalemmal receptors and to keep the numbers of these receptors within reason, while molecular biology may increasingly provide the tools to study the subsequent physiological events. A few years ago, one of us commented (in jest!) that the availability of so many different techniques for examining the properties of alpha‐adrenoceptors may eventually provide the ultimate answer that there are forty‐two subtypes, but that along the way, the original reason for requiring classification might become lost (McGrath, 1983 b).(ABSTRACT TRUNCATED AT 400 WORDS)

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No evidence for differences between pre‐ and post‐junctional α₂‐adrenoceptors

Cited by 28 publications

References 13 publications

A study of ATP as a sympathetic cotransmitter in human saphenous vein

A study of ATP as a sympathetic cotransmitter in human saphenous vein

Investigation of the actions of chloroethylclonidine in rat aorta

Are there more than two types of alpha‐adrenoceptors involved in physiological responses?

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No evidence for differences between pre‐ and post‐junctional α2‐adrenoceptors

Cited by 28 publications

References 13 publications

A study of ATP as a sympathetic cotransmitter in human saphenous vein

A study of ATP as a sympathetic cotransmitter in human saphenous vein

Investigation of the actions of chloroethylclonidine in rat aorta

Are there more than two types of alpha‐adrenoceptors involved in physiological responses?

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No evidence for differences between pre‐ and post‐junctional α₂‐adrenoceptors