Rauwolscine is a valuable tool to study the role of postjunctional α2-adrenoceptor subtypes in rat cutaneous arteries at a physiological temperature of 32°C and after rapid cooling

Rauwolscine, a stereoisomer of yohimbine, is found in the leaves of Rauvolfia canescens L. Both natural products were the prototype for the development of MK912. Rauwolscine, yohimbine and MK912 are antagonists which discriminate between the subtypes of α₂-adrenoceptors, α_2A/D and α_2C. Postjunctional α₂-ARs are involved in Raynaud's phenomenon, an episodic vasosospasm of digital arteries in response to cold. We characterised the α₂-adrenoceptor (α₂-AR) subtype mediating the contractile response to the α₂-AR agonist UK14304 in rat tail arterial rings at 32°C, a physiological temperature for this artery, and after rapid cooling. In non-precontracted arterial rings, UK14304 elicited only slight contractions. However, contractions were markedly enhanced after precontraction with serotonin (5-HT; 10–50 nM). Following precontraction, the contractile UK14304 response was competitively antagonised by rauwolscine (pA₂=8.91±0.06), yohimbine (pA₂=8.54±0.04) and MK912 (pA₂=10.12±0.07) at 32°C. Schild regressions were linear and had slopes of unity indicating that UK14304 activated a homogeneous α₂-AR population. Affinities of rauwolscine, yohimbine and MK912 argue for an involvement of the α_2C-AR subtype in the contractile UK14304 response at 32°C. The presence of α_2C-ARs in this tissue was also confirmed by Western blotting. After rapid cooling (from 37°C to 27°C), the maximal UK14304 response was dramatically enhanced in precontracted arteries; antagonism by rauwolscine was the same before and after cooling (apparent pA₂=8.80–8.90). It is concluded that α_2C-ARs mediate vasoconstriction in cutaneous arteries at 32°C and after rapid cooling. The isolated rat tail artery represents a convenient in vitro bioassay to test novel compounds for the treatment of Raynaud's phenomenon.