Pharmacological characterisation of pre- and postsynaptic alpha-adrenoceptors in dog saphenous vein.

Abstract

1. The pre- and postsynaptic α-adrenoceptors in the dog saphenous vein have been characterised according to their sensitivity to agonists and antagonists. 2. In the presence of uptake 1 and uptake 2 inhibitors, adrenaline, noradrenaline and α-methylnoradrenaline reduced the overflow of radioactivity during field stimulation of saphenous veins pre-loaded with 3H-noradrenaline. Phenylephrine and methoxamine were very weak or inactive. Yohimbine and phentolamine considerably enhanced the stimulationevoked overflow of radioactivity, but prazosin had little effect even at high concentrations. These results identify the presynaptic α-adrenoceptors as belonging to the α2-subtype. 3. Clonidine (up to 10−6 M) did not inhibit the stimulation-evoked overflow of radioactivity; instead it antagonised the effects of exogenous noradrenaline. However, at concentrations of 10−8 M and above clonidine did reduce radioactivity overflow if the uptake inhibitors were omitted from the bathing fluid. These results demonstrate the partial agonist activity of clonidine at presynaptic α2-adrenoceptors. 4. The postsynaptic α-adrenoceptors in the saphenous vein resemble α2-adrenoceptors identified in other tissues. However, α-methylnoradrenaline was more potent, and phenylephrine less potent, than expected. Furthermore, yohimbine exhibited a higher blocking potency at the postsynaptic α-adrenoceptors than has generally been found. 5. In contrast to their effects in other tissues, α-agonist did not greatly reduce contractile responses of the saphenous vein to nerve stimulation, and yohimbine did not enhance them. These effects are discussed in relation to the balance between the pre- and postsynaptic effects of the drugs.