Postjunctional Vascular Alpha-2 Adrenoceptors: Modulation and Interactions

Dunn, William Robert (1989) Postjunctional Vascular Alpha-2 Adrenoceptors: Modulation and Interactions. PhD thesis, University of Glasgow.

Abstract

The work presented herein represents an examination of the alpha-adrenoceptors mediating contractions in isolated vascular preparations from the rabbit and the factors involved in modulating these responses. 1) The alpha-adrenoceptor population in the rabbit isolated lateral saphenous vein, based upon agonist and antagonist potency profiles, could not be ascribed to be either a homogeneous population of either postjunctional alpha1- or alpha2-adrenoceptors, but had characteristics of both. 2) A homogeneous population of postjunctional alpha2-adrenoceptors could be isolated in the lateral saphenous vein using receptor protection experiments with the combination of rauwolscine and phenoxybenzamine. 3) Only limited success was achieved in attempting to isolate a homogeneous population of postjunctional alpha1-adrenoceptors in the lateral saphenous vein using receptor protection experiments with the combination of YM 12617 and phenoxybenzamine. The residual response to NA remaining after this procedure had characteristics of a mixed population of both postjunctional alpha1- and alpha2-adrenoceptors. 4) A comparison of the effects of angiotensin II and Bay K 8644 revealed marked differences in their ability to modulate responses to NA mediated via postjunctional alpha1- and alpha2-adrenoceptors. AII produced a selective enhancement of responses mediated via postjunctional alpha2-adrenoceptors, while the action of Bay K 8644 was not dependent upon receptor subtype. 5) In the lateral saphenous vein after isolation of postjunctional alpha2-adrenoceptors, both Bay K 8644 enhanced responses to NA. The mechanism of this potentiation also appears to differ for these agents. Bay K 8644 enhanced responses mediated via voltage-dependent Ca2+ channels, while AII inhibited the influx of Ca2+ mediated via these channels. 6) The effects of A II on responses mediated via postjunctional alpha2-adrenoceptors, was mimicked by its physiological precursor angiotensin I, suggesting that local vascular production of A II may be important for the facilitatory action of this peptide. 7) Nifedipine, like Bay K 8644, had a non-differential effect on responses to NA mediated via postjunctional alpha1 and alpha2-adrenoceptors in a number of isolated vascular preparations. 8) Under normal experimental conditions, based upon agonist and antagonist potencies, the rabbit isolated distal saphenous artery contains a homogeneous population of postjunctional alpha1-adrenoceptors. 9) In the presence of A II, there was a marked increase in the responsiveness of the distal saphenous artery to UK-14304, which was prazosin-resistant, rauwolscine-sensitive, and so mediated via postjunctional alpha2-adrenoceptors. 10) After attempted isolation of postjunctional alpha2-adrenoceptors in the distal saphenous artery using receptor protection experiments, with the combination of rauwolscine and phenoxybenzamine, no responses were observed. 11) AII uncovered responses to alpha-adrenoceptor agonists after the combination of rauwolscine and phenoxybenzamine. The agonist and antagonist potencies after this protocol were consistent with a homogeneous population of postjunctional alpha2-adrenoceptors. 12) Some of the results in the present study indicate an interaction between postjunctional alpha1- and alpha2-adrenoceptors in vascular smooth muscle. The implications for such an interaction is discussed in detail. Furthermore, evidence is presented demonstrating an interaction between postjunctional alpha2-adrenoceptors and a number of vasoactive agents. 13) Sympathetic neurotransmission in the rabbit isolated distal saphenous artery is the resultant of an interaction between three receptor systems, postjunctional alpha1-and alpha2-adrenoceptors and purinoceptors. alpha1-adrenoceptors are of principal importance, although a role for the two other receptor systems can be demonstrated under the appropriate experimental conditions.

• Item Type: Thesis (PhD)
• Qualification Level: Doctoral
• Keywords: Physiology
• Date of Award: 1989
• Depositing User: Enlighten Team
• Unique ID: glathesis:1989-77932
• Copyright: Copyright of this thesis is held by the author.
• Date Deposited: 30 Jan 2020 15:47
• Last Modified: 30 Jan 2020 15:47
• URI: https://theses.gla.ac.uk/id/eprint/77932