Interaction between prejunctional α₂‐receptors and neuronal transmitter reuptake in small mesenteric arteries from the rat

Abstract

The role of the prejunctional alpha 2-receptors for the response to vaso-constrictor nerve stimulation has been examined before and after inhibition of neuronal transmitter reuptake in mesenteric resistance vessels from the rat. Small arteries (diameter about 200 micron) feeding the jejunum were mounted in a myograph for recording of their isometric wall tension during transmural field stimulation of the intramural nerves. Blockade of prejunctional alpha 2-receptors with 0.01 microM idazoxan (RX 781094) caused a marginal potentiation of the neurogenic response when neuronal reuptake was left intact. Also, inhibition of reuptake alone with 3 microM cocaine had little effect on the response. However, when both alpha 2-receptors and reuptake had been inhibited, a strong enhancement of the neurogenic vasoconstriction was observed. Similar findings were made when yohimbine and LU 3-010 instead were used for alpha 2-blockade and reuptake inhibition, respectively. The results thus indicate that in these resistance arteries the effector response is normally influenced by the combined activity of alpha 2-receptors and uptake, and that failure of one mechanism increases the activity of the other, so as to maintain a largely constant effector response.

Arterial neuroeffector responses in early and mature spontaneously hypertensive rats.

“…It is known that neuronal amine uptake and presynaptic a 2 -adrenergic receptors regulate the net availability of neurotransmitter in the synapse in rat mesenteric arteries. 24 We examined the function of these two systems using cocaine and yohimbine.…”

“…6 Neuronal amine uptake and presynaptic a 2 -adrenergic receptor function are almost certainly not mutually exclusive processes. 24 It is possible that an increase in synaptic norepinephrine concentration resulting from the inhibition of presynaptic aradrenergic receptors could initiate a subsequent increase in neuronal amine uptake to normalize synaptic norepinephrine concentrations. Conversely, the use of cocaine to inhibit the reuptake mechanism would increase synaptic norepinephrine concentration and facilitate autoinhibition of neurotransmitter release by activation of a 2 -receptors presynaptically.…”

Myography of isolated blood vessels: Considerations for experimental design and combination with supplementary techniques

“…Therefore, the absence of an effect of a substance on arterial tone does not exclude the Original trace obtained in an experiment with membrane potential registration in rat saphenous artery. Membrane potential recordings are accepted according to the following criteria: (i) a sharp drop of the potential on cell penetration; (ii) a stable level of the membrane potential recording for at least 30 s; (iii) a return to the zero-potential level after electrode removal; and (iv) a similar electrode resistance before and after the measurement (Nilsson et al, 1998;Rummery and Brock, 2011;Shvetsova et al, 2019).…”

“…Excitation-secretion coupling in vascular nerves is regulated by a number of prejunctional receptors and local non-receptor mechanisms ( Shepherd and Vanhoutte, 1981 ; Aalkjær et al, 2021 ). A simple approach to identify the presynaptic influence of a certain factor is comparing its effects on vasomotor responses to nerve stimulation and to an exogenous transmitter ( Nilsson et al, 1985 ; Martínez et al, 2009 ). However, this is an indirect approach, not without pitfalls.…”

THE EFFECT OF COCAINE AND DESIPRAMINE ON NEURONAL UPTAKE OF [3H]‐NORADRENALINE AND SENSITIVITY TO NORADRENALINE OF RAT MESENTERIC RESISTANCE ARTERIES

“…Washout of prazosin and benextramine then left the al-adrenoceptors exposed and the az-adrenoceptors blocked (Angus et al 1988). Such blockade of a2-adrenoceptors was performed to improve the chances of seeing an effect of uptake1 blockade on the mechanical response under these conditions (Nilsson et al 1985).…”