Frequency- and train length-dependent variation in the roles of postjunctional ?1- and ?2-adrenoceptors for the field stimulation-induced neurogenic contraction of rat tail artery

Abstract

The present paper examines the roles of postjunctional alpha 1- and alpha 2-adrenoceptors for the noradrenaline (NA)-induced neurogenic contractile response to field stimulation mainly with 1-100 pulses at 2 or 20 Hz, in the tail artery of adult normotensive rats. Pharmacological tools were employed to isolate and characterize the alpha 1- and alpha 2-adrenoceptor-mediated components of this response. The degree to which the drugs influenced NA release or reuptake was assessed by their effects on the electrochemically determined, stimulation-induced rise in the NA concentration at the innervated outer surface of the media. This response was unaffected by alpha,beta-methylene ATP (10 microM) or suramin (500 microM), added to desensitize or block P2-purinoceptors, respectively prazosin (0.1 microM) or SK&F 104078 (6-chloro-9-[(3-methyl-2-butenyl)oxyl]-3-methyl- 1H-2,3,4,5-tetrohydro-3-benzazepine, 0.1 microM), used to block postjunctional alpha 1- and alpha 2-adrenoceptors respectively, nifedipine (10 microM), blocker of Ca2+ influx through L-type channels, and ryanodine (10 microM), which blocks mobilization of Ca2+ from intracellular stores; it was moderately enhanced by yohimbine (0.1 microM), blocker of pre- and postjunctional alpha 2-adrenoceptors, and strongly enhanced by cocaine (3 microM) or desipramine (1 microM), blockers of NA reuptake. Judging from their inhibitory effects on the contractile responses to the alpha 1- and alpha 2-adrenoceptor agonists, phenylephrine and xylazine, prazosin (0.1 microM) and SK&F 104078 (0.1 microM) could be used to selectively block alpha 1- and alpha 2-adrenoceptors respectively, while yohimbine (0.1 microM) was less selective, strongly depressing alpha 2- and slightly depressing alpha 1-adrenoceptor-mediated responses. The alpha 1-adrenoceptor-mediated component of the contractile response to short trains at 20 Hz was fast in onset, brief in duration and abolished by ryanodine; that mediated by alpha 2-adrenoceptors was more delayed, prolonged and insensitive to ryanodine. Both components were dose-dependently depressed by nifedipine (0.1-10 microM). The small contractile responses to single pulses, or up to 50 pulses at 2 Hz, or short train (< 4 pulses) at 20 Hz, were more markedly depressed by 0.1 microM yohimbine or SK&F 104078 than by 0.1 microM prazosin and, hence, mediated mainly by alpha 2-adrenoceptors. The reverse was true of the much larger response to longer trains at 20 Hz, which thus probably was mediated mainly by alpha 1-adrenoceptors.(ABSTRACT TRUNCATED AT 400 WORDS)

Dual contractile effects of ATP released by field stimulation revealed by effects of α,β‐methylene ATP and suramin in rat tail artery

“…We have also reported that a,-MeATP strongly increased the amplitude of the NA-mediated neurogenic contraction. The potentiating effect was more marked on the al-than on the X2-adrenoceptor-mediated component of this response; during stimulation at 20 Hz it was inversely related to the train length 1993a). A similar potentiating effect of oE,j-MeATP on the neurogenic contraction has been reported to occur in other vascular tissues and in vas deferens (Bulloch et al, 1990;MacDonald et al, 1992).…”

“…These effects probably do not interfere with the neurogenic contraction in rat tail artery, however, because the P2Y-purinoceptor antagonist reactive blue 2 (Burnstock & Warland, 1987) did not at 10-50 JM concentrations significantly affect the neurogenic contraction of rat tail artery caused by 10 pulses at 20 Hz, or the enhancing effect of a,-MeATP on the contraction (n = 3, not shown), and because P2z-purinoceptors do not seem to exist on smooth muscle cells (see Gordon, 1986). The following findings in the present study indicate that the effects of suramin were due to block of the P2x-purinoceptor- (Bao et al, 1989;1993a Leff et al, 1990). Addition of the K+-channel blocker, tetraethylammonium, greatly amplified the ATP-as well as NA-induced components of the neurogenic contraction, probably by dramatically increasing the release of both NA and ATP Stjiirne et al, 1990) and the excitability of the smooth muscle (Haeusler & Thorens, 1980 (Bao et al, 1993b) and that the ATP-mediated contractile response faded rapidly during long high frequency trains (Bao et al, 1993b), probably as a result of decline in per pulse release of ATP .…”

“…Subsequent addition of m,P-MeATP z E (10 pM) itself caused a contraction (peak value 6.5 ± 0.3 mN, n = 51) which subsided within 20-30 min. Now the small residual neurogenic contraction in the presence of prazosin and yohimbine was almost abolished (not shown, but see Figure 5 in Bao et al, 1993a Figures 2,3); the IC50 for this effect was 75 pLM ( Figure 3). …”

“…The neurogenic contraction has been thought to be mediated exclusively by NA (Cheung, 1984;Medgett & Langer, 1984;Vidal et al, 1986), but we have found that the initial phase of this response was inhibited by a,-methylene ATP (a,-MeATP), a P2x-purinoceptor desensitizing agent (Kasakov & Burnstock, 1983;Sneddon & Burnstock, 1984), and hence was mediated by ATP (Bao et al, 1989;1990;1993a). We have also reported that a,-MeATP strongly increased the amplitude of the NA-mediated neurogenic contraction.…”

Rilmenidine reveals differences in the pharmacological characteristics of prejunctional α2‐adrenoceptors in the guinea‐pig, rat and pig

“…However, in the latter preparation the sensitivity of the response to the selective a 2 -adrenoceptor antagonist, RX-811059 (Mallard et al, 1992), indicates a role for postjunctional a 2 -adrenoceptors in addition to a 1 -adrenoceptors. These ®ndings agree with earlier reports by several other groups (Medgett et al, 1983;Rajanayagam et al, 1990;Bao et al, 1993). In the guinea-pig isolated ileum, a well recognized model of cholinergic neurotransmission, the electrically-evoked responses were abolished by the muscarinic receptor blocker atropine.…”