Effect of duration and frequency of stimulation on the presynaptic inhibition by ?-adrenoceptor stimulation of the adrenergic transmission

I The spinal sympathetic outflow to the eyelid, heart, splanchnic blood vessels, vas deferens and anococcygeus muscle was stimulated in pithed rats. 2 Clonidine inhibited sympathetic outflow to all of the tissues studied. The inhibitory effects of clonidine on cardiac nerves and hypogastric nerves were antagonized by phentolamine. 3 Clonidine produced a postsynaptic a-adrenoceptor agonist action on the eyelid, splanchnic blood vessels and the anococcygeus muscle. These effects were also antagonized by phentolamine. 4 The effects of clonidine, naphazoline and oxymetazoline on pre-and postsynaptic a-adrenoceptors were determined. 5 The presynaptic a-adrenoceptors employed were situated in either the sympathetic cardiac or hypogastric nerve terminals. Increases in diastolic blood pressure were used to assess concurrent postsynaptic a-adrenoceptor agonist activity. 6 The presynaptic a-adrenoceptor agonist potencies of clonidine, naphazoline and oxymetazoline were very similar on cardiac nerve terminals whereas on the hypogastric nerve terminals oxymetazoline was about 6 times more potent than either naphazoline or clonidine. 7 The results support the view that presynaptic a-adrenoceptors regulate transmitter release in sympathetic nerves. There appear to be subtle differences between the presynaptic a-adrenoceptors of different sympathetic nerve endings.

Section: Discussionmentioning

confidence: 67%

Inhibitory Effects of Clonidine on Responses to Sympathetic Nerve Stimulation in the Pithed Rat

Doxey

Everitt

1977

“…The resolution of this problem requires the ability to separate the two transmission processes by (1) selective blockade of the effector response and (2) detection of the transmitter output. Since neither of these manoeuvres is yet possible for the uncharacterized 'non-adrenergic' component, analysis is limited by the following factors: (a) Adrenergic response Since a-adrenoceptor blockers such as yohimbine and phentolamine, can increase the nerve-induced output of noradrenaline from vas deferens at frequencies of 2 to 10 Hz (Stjarne, 1973;Vizi et al, 1973), it is likely that the doses which produced increased responses at 2 and 10 Hz in the present study increased the output of noradrenaline from the adrenergic nerves. At concentrations below the threshold for post-junctional blockade it is likely that more noradrenaline is available to act on the smooth muscle but the contribution to the overall response of the NA cannot be determined since there is no method which selectively removes the 'nonadrenergic' component and the latter may also have been modified by the a-blocker (see below).…”

Section: Resultsmentioning

confidence: 99%

“…In the vas deferens it is well established that the height of the contractile response to nerve stimulation is resistant to reduction by a-adrenoceptor antagonists (Boyd, Chang & Rand, 1960;Ambache & Zar, 1971) at concentrations which increase the nerveinduced output of NA (Stjarne, 1973;Vizi, Somogyi, Hadhazy & Knoll, 1973). In order to explain this it has been suggested that the effector response is adrenergic but resistant to post-junctional blockade (Swedin, 1971;Furness, 1974) or alternatively due to a separate set of 'non-adrenergic' nerves (Ambache © Macmillan Journals Ltd 1979& Zar, 1971.…”

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.

“…These propranolol-resistant effects of isoprenaline were antagonized by metoclopramide and phentolamine and the pA2 values obtained (5.3 and 7.7) were identical to those obtained when clonidine was used as the agonist, indicating that isoprenaline (>0.5 gM) may activate presynaptic a-adrenoceptors. Interestingly, isoprenaline (0.5 to 1 riM) hyperpolarizes rat sympathetic ganglia prep-arations by an action which is antagonized by phentolamine but not by propranolol (Brown & Caulfield, 1979), an effect on 'a2'-adrenoceptors (Berthelson & Pettinger, 1977;Langer, 1977 (Vizi et al, 1973;Jenkins et al, 1977). Metoclopramide, by acting as an antagonist at these receptors, would prevent the inhibition, thereby augmenting the contraction.…”

Section: Discussionmentioning

confidence: 99%

Effects of Metoclopramide and Isoprenaline in the Rat Vas Deferens; Interactions With Α‐adrenoceptors

Spedding

1980

3 From these results it is concluded that metoclopramide (2.8 to 280 pM) is a presynaptic a-adrenoceptor antagonist in the rat vas deferens.4 Following,-adrenoceptor blockade with (±)-propranolol (3.3 gM), (--isoprenaline (0.47 to 14 gM) inhibited responses to field stimulation but not to phenylephrine. These propranolol-resistant effects of isoprenaline were antagonized by metoclopramide (2.8 to 280 pM) and by phentolamine (0