Preferential blockade of presynaptic α-adrenoceptors by yohimbine

1 The effects of endogenous noradrenaline released by tyramine and the influence of depletion of the tissue noradrenaline with reserpine and/or oa-methyl-p-tyrosine on the twitch responses of the field-stimulated mouse vas deferens have been studied.2 Tyramine (10-40 gM) inhibited the twitch responses to field stimulation and failed to produce a contraction. The inhibition decreased as the rate of stimulation increased.3 The inhibition produced by tyramine was antagonized by cocaine (10 PM) and by yohimbine (10 nM), which indicated that it was produced by released noradrenaline acting on presynaptic a-adrenoceptors. 4 Depletion of the tissue noradrenaline by 39% by blockade of the synthesis of noradrenaline with a-methyl-p-tyrosine, was without effect on the twitch response but it reduced the inhibitory effect of tyramine. 5 Depletion of the tissue noradrenaline by 96.5% with reserpine alone and by 99.4%, with a combination of reserpine and ax-methyl-p-tyrosine, reduced the twitch responses by approximately 66% and virtually abolished the inhibition produced by tyramine. It also increased the rate of decline of the responses when the tissue was continuously stimulated. The remaining twitch was not antagonized by phenoxybenzamine (15 gM).6 Residual twitches were bigger in tissues depleted by 99.4% than in those depleted by only 96.5%. This difference was eliminated in the presence of yohimbine (128 nM). 7 It is concluded that inhibition of the twitch responses by tyramine is produced by stimulation of presynaptic a-adrenoceptors and that the twitch response is associated with stimulation of the sympathetic neurone, but that it is not mediated by postsynaptic a-adrenoceptors.

Section: Dicussionsupporting

confidence: 75%

The Effects of Release and Depletion of Endogenous Noradrenaline on the Transmission of Impulses in the Mouse Vas Deferens

Marshall

Nasmyth

Shepperson

1978

“…These drugs could act by blockade of the antilipolytic a -adrenoceptor on fat cell membranes (Arner & Ostman, 1976;Fain & Garcia-Sainz, 1983;Berlan & Lafontan, 1985;Mauriege et al, 1987). They could also activate sympathetic tone either through actions on the central nervous system (Papeschi & Theiss, 1975) or indirectly by blockade of the presynaptic a2-adrenoceptors located on the sympathetic nerve endings (Starke et al, 1975;Langer, 1980) or by a mixture of both actions. These mechanisms could be additive in the improvement of lipid mobilization.…”

Section: Introductionmentioning

confidence: 99%

Lipomobilizing effects of procaterol and yohimbine in the conscious dog: comparison of endocrinological, metabolic and cardiovascular effects

Valet¹,

Taouis²,

Tran³

et al. 1989

provoked an equivalent increase in plasma non-esterified fatty acids (+ 100%). Procaterol, but not yohimbine, induced hyperglycaemia (+ 120%). Plasma insulin was weakly enhanced by yohimbine (+ 120%) as compared to the increase given by procaterol (+ 500%). 4 Both drugs stimulated sympathetic nervous system activity, as indicated by the increased plasma noradrenaline concentration, but only yohimbine increased the plasma adrenaline level. 5 Cardiovascular measurements indicated that procaterol strongly enhances heart rate and transiently decreases mean blood pressure. Yohimbine exhibits a weaker effect on heart rate and slightly increases mean blood pressure. 6 The present work clearly indicates that lipid mobilization is enhanced during fasting in the dog by selective fl2-adrenoceptor stimulation or by Cc2-adrenoceptor blockade. This enhanced lipolytic effect may result either from a direct action of the drugs on the adrenoceptors of fat cells or from an activation of the sympathetic nervous system. Procaterol suffers major limitations since it strongly increases heart rate, immunoreactive insulin and glycaemia. On the other hand, yohimbine induces only minor modifications both in cardiovascular and endocrinological parameters.

“…The principal evidence comes from the observation that in noradrenergically innervated tissues, the overflow of noradrenaline (NA) on nerve stimulation, taken to be an index of transmitter release, can be reduced by a-adrenoceptor agonists (Starke, 1972a, b;Langer, Enero, Adler-Graschinsky & Stefano, 1972) and increased by a-adrenoceptor antagonists (Brown & Gillespie, 1957;Kirpekar & Puig, 1971;Haggendal, Johansson, Jonason & Ljung, 1972;Dubocovich & Langer, 1974;Starke, Borowski & Endo, 1975). More recently it has been suggested that agonists (Starke, Endo & Taube, 1975;Drew, 1977) and antagonists Drew, 1976) display a degree of selectivity for pre-and postsynaptic ' Present address: Department of Anatomy, University College, London.…”

Section: Introductionmentioning

confidence: 99%

The EFFECTS OF Α‐ADRENOCEPTOR AGONISTS AND ANTAGONISTS ON RESPONSES OF TRANSMURALLY STIMULATED PROSTATIC AND EPIDIDYMAL PORTIONS OF THE ISOLATED VAS DEFERENS OF THE RAT

Brown

McGrath

Summers

1979

1 The effects of a-adrenoceptor agonists and antagonists on contractile responses of transmurally stimulated prostatic and epididymal portions of the rat isolated vas deferens were examined. 2 Responses to single stimuli consisted of two phases, the first predominant in the prostatic and the second in the epididymal portion. The first phase was resistant to a-adrenoceptor antagonists but the second was reduced in a dose-related manner in the order of potency prazosin > azapetine > phentolamine > labetalol > yohimbine. 3 Both phases of the response to a single stimulus were reduced by clonidine but only the first could be reliably restored by yohimbine. 4 Trains of transmural stimuli produced biphasic. responses, an early rapid component predominant in the prostatic and a slower secondary component predominant in the epididymal portion. The effects of a-adrenoceptor antagonists on these responses were complex. Prazosin produced the most straightforward inhibition of responses with relative resistance of the early rapid component. Only yohimbine and phentolamine produced increases in responses which could be pre-junctional in origin. 5 The a-adrenoceptor agonists, oxymetazoline and clonidine, reduced while phenylephrine increased responses to trains of stimuli. 6 These results are discussed in relation to the nature of the innervation of rat vas deferens and the usefulness of the preparation in pharmacological tests for activity at a-adrenoceptors.