An examination of the postjunctional α‐adrenoceptor subtypes for (−)‐noradrenaline in several isolated blood vessels from the rabbit

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Section: Drugssupporting

confidence: 58%

Examination of the role of inhibition of cyclic AMP in α₂‐adrenoceptor mediated contractions of the porcine isolated palmar lateral vein

Wright

Harling

Kendall

et al. 1995

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“…Conversely, rauwolscine (1pM), at a concentration approximately 100 times greater than that equivalent to its pA2 value at postjunctional a2-adrenoceptors in the rabbit ear vein (Daly et al, 1988b) and its dissociation constant in the lateral saphenous vein after isolation of postjunctional a2-adrenoceptors (Daly et al, 1988a), produced only a small rightward displacement of the CCRC to NA in this preparation. The estimated -log KB value for rauwolscine (6.32) in the rabbit distal saphenous artery is therefore slightly higher, but not dissimilar to its reported pA2 value at postjunctional ax-adrenoceptors in other rabbit vascular preparations, such as the thoracic aorta (6.1) and ear artery (5.5) (Daly et al, 1988c).…”

Section: Effect Of Other Agents On Responses To Uk-14304mentioning

confidence: 49%

Postjunctional α‐adrenoceptors in the rabbit isolated distal saphenous artery: indirect sensitivity to prazosin of responses to noradrenaline mediated via postjunctional α₂‐adrenoceptors

Dunn

McGrath

Wilson

1991

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1Under normal experimental conditions, the rabbit isolated distal saphenous artery appears to contain a homogeneous population of postjunctional ae-adrenoceptors. Prazosin 4 The responses to NA, after the protection protocol, in the presence of All, were susceptible to the selective a2-adrenoceptor antagonist, rauwolscine (1 M), but resistant to the selective a,-adrenoceptor antagonist prazosin (0.1 pM). Furthermore, the combination of rauwolscine (1 M) and prazosin (0.1 IpM) was no more effective in blocking responses to NA than was rauwolscine (1 pM) alone. These results are consistent with the presence of a homogeneous population of postjunctional oc2-adrenoceptors. 5 Inducing a small degree of tone with a low concentration of the selective ac-adrenoceptor agonist, phenylephrine, markedly increased the threshold sensitivity to the selective a2-adrenoceptor agonist UK-14304, in a manner analogous to that seen with All. 6 The results in the present study indicate that responses mediated via postjunctional a2-adrenoceptors in the rabbit isolated distal saphenous artery are dependent upon a degree of vascular smooth muscle stimulation by some other receptor system. It is hypothesized that under normal experimental conditions, this function is fulfilled by stimulation of al-adrenoceptors, while after ax-adrenoceptor blockade the necessary positive influence can be provided by stimulation of All receptors. The implications for such an interaction between postjunctional a-adrenoceptor subtypes in demonstrating prazosin-resistant, rauwolscine-or yohimbine-sensitive responses in isolated blood vessels is discussed.

“…The existence of these two subclasses has been demonstrated frequently by functional studies on arterial resistance in vivo, but the presence of a2-adrenoceptors has been more difficult to demonstrate in vitro (see Agrawal et al, 1987) with functionality often only being observed in the presence of an ancillary spasmogen (Daly et al, 1988;Dunn et al, 1991). However, overt a2-adrenoceptor mediated contractions have been observed in a range of non-conduit/distal arteries and veins not generally used for routine experimentation, such as human arterioles (Nielsen et al, 1989), canine saphenous vein (Flavahan & Vanhoutte, 1986), rabbit saphenous vein (Daly et al, 1988), and feline middle cerebral artery (Fredholm et al, 1985). A comparative study by Nielsen et al (1991) examined the pharmacological characteristics of x-adrenoceptor-mediated contractions to noradrenaline in similar sized mesenteric arteries (200 fym diameter) from the rat, rabbit, pig and man and found a2-adrenoceptor-mediated contractions detectable only in porcine and human blood vessels.…”

Section: Introductionmentioning

confidence: 99%

The relationship between density of α‐adrenoceptor binding sites and contractile responses in several porcine isolated blood vessels

Wright

Blaylock

Kendall

et al. 1995

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1 The aim of this study was to investigate constrictor x-adrenoceptors in three isolated blood vessles of the pig, the thoracic aorta (TA), the splenic artery (SA) and marginal ear vein (MEV) and then compare the functional response with the densities of a,-and M2-adrenoceptor binding sites in these and several other porcine vascular tissues, palmar common digital artery (PCDA), palmar lateral vein (PLV) and ear artery (EA).2 Noradrenaline (NA), phenylephrine (PE) and UK14304 (all at 0.03-10gM) elicited concentrationdependent contractions in the TA and MEV, with a rank order of potency of UK14304>NA>PE. UK14304 produced maximal responses which were 58% (TA) and 65% (MEV) of that of NA. In the SA, UK14304 and PE produced maximal responses which were less than 10% and 50% of the NA-induced maximal response respectively, with an order of potency of NA>PE. In the SA, NAinduced contractions were competitively antagonized by prazosin (pA2 = 8.60 ± 0.15). Further, rauwolscine (1-1O M) antagonized NA-induced contractions with an apparent pKB of 6.09 ± 0.11 (n = 6), indicating an action at al-adrenoceptors. The combination of the two antagonists at concentrations selective for al-(0.1 JLM) and a2-adrenoceptors (1 J4M) had no greater effect than either antagonist alone.This suggests that the SA expresses only post-junctional a1-adrenoceptors.3 In the TA, prazosin produced non-parallel shifts in the NA-induced CRC and this was also observed with rauwolscine, where reductions in the maximal responses were also observed. In the MEV, prazosin was largely inactive in antagonizing NA-induced contractions. In both these vessels a combination of these two antagonists had a greater effect than either alone, indicating the presence of functional a,-and M2-adrenoceptors. The post-junctional x2-adrenoceptors in all of these vessels were resistant to prazosin, suggesting the a2-adrenoceptor to be of the a2A/2D subtype. mg-', n = 4), followed by the PCDA (256.7 ± 22.7 fmol mg', n = 4), the PLV and SA having approximately equal density (143.6 ± 3.9 and 159.1 ± 7.0 fmol mg-' respectively, n = 4 for both), followed by the EA (91.3 ± 10.5 fmol mg-', n = 3) and the MEV had the lowest density (48.9 ± 11.4 fmol mg-', n = 3).7 In saturation studies using [3H]-RX821002, all tissues produced single site saturation curves with no differences in the Kd values (range 1.31 ± 2.16 nM) but the highest densities were found in the TA and MEV (545.3 ± 36.2 and 531.0 ± 40.9 fmol mg-' respectively), followed by the PLV (418.4 ± 39.4 fmol mg-'), then the EA (266.3 ± 40.0 fmol mg-'), and low densities of [3H]-RX821002 binding being found in the PCDA and SA (155.9 ± 18.1 and 117.5 ± 19.3 fmol mg-' respectively). 8 The pattern of binding site distribution for ol-and C2-adrenoceptors is in reasonable agreement with functional studies carried out in these porcine vascular tissues; the TA has the highest densities of a,-and X2-adrenoceptors; in the SA and PCDA there is a predominance (although small) of al-adrenoceptor binding sites, the reverse of which is obse...