SELECTIVITIES OF SOME AGONISTS ACTING AT α₁‐ AND α₂‐ADRENORECEPTORS IN THE RAT VAS DEFERENS

Abstract

In this paper, estimates of the selectivities of a series of twelve sympathomimetic agents acting at postjunctional alpha 1- and prejunctional alpha 2-adrenoreceptors were investigated, using epididymal and prostatic segments of the rat vas deferens. The relative order of potency for the twelve agonists at prejunctional alpha 2-adrenoreceptors mediating inhibition of field-stimulation-induced contractions in the prostatic segment of the vas deferens was: clonidine greater than (-)-adrenaline greater than xylazine greater than or equal to (-)-noradrenaline greater than (+)-adrenaline greater than dopamine greater than or equal to phenylephrine greater than or equal to metaraminol greater than or equal to (+)-noradrenaline greater than (-)-isoprenaline greater than methoxamine greater than (+)-isoprenaline. The relative order of potency for the agonists at postjunctional alpha 1-adrenoreceptors mediating contraction of smooth muscle in epididymal segments of the vas deferens was: (-)-adrenaline greater than or equal to (-)-noradrenaline greater than phenylephrine greater than clonidine greater than or equal to (+)-adrenaline greater than or equal to methoxamine greater than or equal to (+)-noradrenaline greater than or equal to metaraminol greater than or equal to dopamine greater than or equal to (-)-isoprenaline greater than or equal to xylazine; (+)-isoprenaline was inactive. (+)-Noradrenaline, the stereoisomers of adrenaline and isoprenaline, dopamine, clonidine, xylazine and metaraminol displayed alpha 2-selectivity whereas phenylephrine and methoxamine displayed alpha 1-adrenoreceptor selectivity. (-)-Noradrenaline possessed a similar potency at both alpha 1- and alpha 2-adrenoreceptors thus making it non-selective by the criteria used in this study.(ABSTRACT TRUNCATED AT 250 WORDS)

Sympathetic co‐transmission to the cauda epididymis of the rat: characterization of postjunctional adrenoceptors and purinoceptors

“…Despite the omission of propranolol in the present experiments, the EC30 obtained for isoprenaline in this study was similar to that obtained by Starke (1981) and Leedham & Pennefather (1986) both of whom included propranolol in their incubation media.…”

“…6-Oestradiol was dissolved in ethanol. A stock solution of prazosin was made by initially dissolving it in glycerol and then making it up to volume with a 5% w/v dextrose solution (see Leedham & Pennefather, 1986 Fige 3 Mean log concentration-response curves for: adrenaline applied sequentially to isolated cauda epididymis segments (0) Effects of inhibitors ofuptake and propranolol on concentration-response curves to adrenaline Adrenaline produced concentration-dependent tonic contractions of isolated preparations of the rat cauda epididymis. The mean negative log molar EC5o (i.e.…”

“…6-Oestradiol was dissolved in ethanol. A stock solution of prazosin was made by initially dissolving it in glycerol and then making it up to volume with a 5% w/v dextrose solution (see Leedham & Pennefather, 1986). Dilutions to the required con- (0) (10Hz, 1 ms, 60V, for lOs every lOOs) of isolated preparations of the rat cauda epididymis.…”

“…It is well documented that the contractions of the rat vas deferens evoked by nerve stimulation are mediated through the release of noradrenaline and of adenosine 5'-triphosphate (ATP) which act post-junctionally at ar-adrenoceptors (van Rossum, 1965;Leedham & Pennefather, 1986) and P2x-purinoceptors (Burnstock & Kennedy, 1985) respectively. Little research has been carried out on neurotransmission to the cauda epididymis.…”

Dopamine acting at D1-like, D2-like and α1-adrenergic receptors differentially modulates theta and gamma oscillatory activity in primary motor cortex

“…Furthermore, DA/α1 subunits potentially form heteromultimeric receptor complexes which could display unique signalling and activation properties [81,82,83,84]. The robust effects of DA acting through α1 receptors in M1 is surprising considering DA has only 1/50 th the affinity of noradrenaline for the α1 receptor [85]. It may be that DA has a greater affinity for a DA/α1 heteromultimeric receptor than for homomeric α1 receptors.…”