Pre- and postsynaptic components in effect of drugs with α adrenoceptor affinity

Starke, Klaus; Endo, Takahiko; Taube, H. D.

doi:10.1038/254440a0

Cited by 80 publications

(29 citation statements)

References 11 publications

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“…The postjunctional excitatory al-and inhibitory P-adrenoceptors could be detected not only in the terminal but also in the proximal parts of the ileum (Bauer, 1981), in agreement with the findings of Anderson & Lees (1976) and Wikberg (1978). It has been suggested that a pharmacological difference exists between inhibitory prejunctional and excitatory postjunctional adrenoceptors, as in other smooth muscle preparations (Langer, 1974;Starke, Endo & Taube, 1975;Drew, 1977a) and that an inhibitory postjunctional aadrenoceptor, which is as yet uncharacterized, is also present (Bauer, 1981).…”

Section: Introductionsupporting

confidence: 85%

Distribution and Types of Adrenoceptors in the Guinea‐pig Ileum: The Action of Α‐ and Β‐adrenoceptor Blocking Agents

Bauer¹

1982

British J Pharmacology

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Czechoslovakia1 Transmurally stimulated segmeQts of the guinea-pig ileum have been used to analyse the different adrenoceptors in the terminal (0 to 3 cm) and the proximal (> 50 cm from the ileocaecal valve) ileum.2 The prejunctional adrenoceptors (located on the final, cholinergic, motor nerve terminals) and postjunctional adrenoceptors (located on the smooth muscle membrane) have been characterized according to their sensitivity to a-and 0-agonists and antagonists. 3 Phentolamine, phenoxybenzamine and yohimbine, in concentrations of 0.1 AM, transiently enhanced (up to 10%) the twitch response. At higher concentrations all the a-and P-antagonists studied depressed the neurogenic twitches and relaxed the smooth muscle.4 The twitch-inhibitory effects of adrenoceptor agonists (noradrenaline, adrenaline and ephedrine) were not antagonized by phenoxybenzamine (0.1, 0.5 and 1 tM), carbidine (0.5, 1 and 5 piM) and propranolol (0.5, 1 and 5 pM); however, they were depressed by phentolamine (0.1, 0.5, 1.25 and 5 pM) and yohimbine (0.25, 0.5 and 5pM). 5 The smooth muscle contractions induced by noradrenaline and adrenaline in the terminal ileum and by phenylephrine in both the terminal and proximal ileum were antagonized by phenoxybenzamine, carbidine and phentolamine but were not influenced by yohimbine and propranolol. 6 The smooth muscle relaxations of the proximal ileum induced by noradrenaline, adrenaline and ephedrine were inhibited by yohimbine, phentolamine, carbidine and phenoxybenzamine, and the isoprenaline-induced relaxation was antagonized by propranolol. 7 All the agonists studied, except phenylephrine, elicited relaxations of the acetylcholine-induced sustained contraction of both proximal and terminal ileum. The relaxation induced by isoprenaline was antagonized by propranolol, and the effects of noradrenaline and ephedrine by yohimbine.8 It is concluded that in the guinea-pig ileum there are postsynaptic P-adrenoceptors and at least two types of a-adrenoceptors: al-excitatory postjunctional adrenoceptors activated by phenylephrine, noradrenaline and adrenaline and antagonized by phenoxybenzamine, carbidine and phentolamine; a2-inhibitory prejunctional adrenoceptors activated by ephedrine, noradrenaline and adrenaline and inhibited by yohimbine and phentolamine. The inhibitory postjunctional aadrenoceptors are more close to the a2-adrenoceptors, since they were stimulated predominantly by ephedrine and noradrenaline and inhibited by yohimbine. 9 It has been shown that all a-adrenoceptor subtypes are to be found at every distance (0 to 70 cm) from the ileocaecal valve and that they can be activated in the resting or in the acetylcholinecontracted states.

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Section: Introductionsupporting

confidence: 85%

Distribution and Types of Adrenoceptors in the Guinea‐pig Ileum: The Action of Α‐ and Β‐adrenoceptor Blocking Agents

Bauer¹

1982

British J Pharmacology

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“…Using the field-stimulated pulmonary artery, Starke, Endo & Taube (1975) showed that phenylephrine preferentially stimulated postsynaptic a-adrenoceptors, whereas the presynaptic receptors were preferentially stimulated by clonidine (Starke, Montel, Gayk & Merker, 1974). This could certainly account for the results reported here and would explain why propranolol did not block the inhibition of the twitch response produced by noradrenaline.…”

Section: Discussionsupporting

confidence: 52%

Α‐adrenoceptors in the Mouse Vas Deferens and Their Effects on Its Response to Electrical Stimulation

Marshall

Nasmyth

Nicholl

et al. 1978

British J Pharmacology

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1 Noradrenaline (ID50, 0.75 pM) and clonidine (ID50, 2.8 nM) produced a dose-related inhibition of the twitch response of the isolated vas deferens of the mouse to electrical stimulation, their effectiveness decreasing as frequency of stimulation increased from 0.2 to 16 hertz. 2 Phenylephrine (1.0-3.0 pM) produced a dose-related contraction of the mouse isolated vas deferens and potentiated the responses to field stimulation. 3 Yohimbine (10 nM) antagonized the inhibitory effects of noradrenaline and clonidine, but had no effect on the motor activity of phenylephrine. At a concentration of 128 nM yohimbine potentiated the twitch response by 110% at 1 Hz, but its effectiveness decreased with increasing frequency of stimulation up to 16 hertz.4 Thymoxamine (0.3 gM) antagonized the effects of phenylephrine, but not those of clonidine.5 From a consideration of the known characteristics of pre-and postsynaptic a-adrenoceptors, it is concluded that the inhibitory effect of noradrenaline is produced by stimulation of the former and the effects of phenylephrine by stimulation of the latter.

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“…Another potential mechanism for the present findings is the presynaptic autoregulatory feedback inhibition of NE on the sympathetic outflow (14,26). The exact mechanism of this feedback regulation is not completely defined, but most probably it is mediated by ␣ 2 -receptors (20).…”

Section: Discussionmentioning

confidence: 92%

“…This attenuation of sympathetic outflow does not seem to be merely a result of baroreceptor feedback due to elevated blood pressure, because these alterations remained the same after the return of blood pressure to the baseline level after ␣-adrenergic blockade with Phe. Furthermore, cardiovagal BRS did not change during the NE infusion with Phe, as analyzed by the cross-spectral method (using both LF and HF spectral bands), suggesting that the inhibitory effects of NE on LF oscillation of R-R intervals and MSNA are not explained by altered baroreflex gain but perhaps by a presynaptic autoregulatory feedback mechanism (26) or some other mechanism that is not inhibited by ␣-adrenergic blockade.…”

Section: Discussionmentioning

confidence: 99%

Feedback effects of circulating norepinephrine on sympathetic outflow in healthy subjects

Tulppo¹,

Huikuri²,

Tutungi³

et al. 2005

American Journal of Physiology-Heart and Circulatory Physiology

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The amplitude of low-frequency (LF) oscillations of heart rate (HR) usually reflects the magnitude of sympathetic activity, but during some conditions, e.g., physical exercise, high sympathetic activity results in a paradoxical decrease of LF oscillations of HR. We tested the hypothesis that this phenomenon may result from a feedback inhibition of sympathetic outflow caused by circulating norepinephrine (NE). A physiological dose of NE (100 ng ⅐ kg Ϫ1 ⅐ min Ϫ1 ) was infused into eight healthy subjects, and infusion was continued after ␣-adrenergic blockade [with phentolamine (Phe)]. Muscle sympathetic nervous activity (MSNA) from the peroneal nerve, LF (0.04 -0.15 Hz) and high frequency (HF; 0.15-0.40 Hz) spectral components of HR variability, and systolic blood pressure variability were analyzed at baseline, during NE infusion, and during NE infusion after Phe administration. The NE infusion increased the mean blood pressure and decreased the average HR (P Ͻ 0.01 for both). MSNA (10 Ϯ 2 vs. 2 Ϯ 1 bursts/min, P Ͻ 0.01), LF oscillations of HR (43 Ϯ 13 vs. 35 Ϯ 13 normalized units, P Ͻ 0.05), and systolic blood pressure (3.1 Ϯ 2.3 vs. 2.0 Ϯ 1.1 mmHg 2 , P Ͻ 0.05) decreased significantly during the NE infusion. During the NE infusion after PHE, average HR and mean blood pressure returned to baseline levels. However, MSNA (4 Ϯ 2 bursts/ min), LF power of HR (33 Ϯ 9 normalized units), and systolic blood pressure variability (1.7 Ϯ 1.1 mmHg 2 ) remained significantly (P Ͻ 0.05 for all) below baseline values. Baroreflex gain did not change significantly during the interventions. Elevated levels of circulating NE cause a feedback inhibition on sympathetic outflow in healthy subjects. These inhibitory effects do not seem to be mediated by pressor effects on the baroreflex loop but perhaps by a presynaptic autoregulatory feedback mechanism or some other mechanism that is not prevented by a nonselective ␣-adrenergic blockade.heart rate dynamics; catecholamines; blood pressure oscillation LOW-FREQUENCY (LF) oscillations of heart rate (HR) have been proposed to be under the control of sympathetic and vagal outflow. The normalized LF component of HR variability increases during most laboratory interventions that result in increased sympathetic outflow, including passive head-up tilt, moderate exercise, and nitroprusside infusion (15-18). Paradoxically, some physiological and pathological conditions known to increase sympathetic outflow have involved a marked reduction in the LF power spectral component and the LF-to high frequency (HF) ratio, for example, heavy physical exercise, passive head-up tilting preceding syncope, and severe heart failure (9, 31, 33).The physiological background of the decreased LF spectra of R-R intervals during increased sympathetic outflow has not been fully elucidated. Resetting of baroreflex circulatory regulation has been proposed as one possible reason. Other speculated reasons are saturation of the LF oscillatory system during high sympathetic activity or a central effect of neurohumoral excit...

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Pre- and postsynaptic components in effect of drugs with α adrenoceptor affinity

Cited by 80 publications

References 11 publications

Distribution and Types of Adrenoceptors in the Guinea‐pig Ileum: The Action of Α‐ and Β‐adrenoceptor Blocking Agents

Distribution and Types of Adrenoceptors in the Guinea‐pig Ileum: The Action of Α‐ and Β‐adrenoceptor Blocking Agents

Α‐adrenoceptors in the Mouse Vas Deferens and Their Effects on Its Response to Electrical Stimulation

Feedback effects of circulating norepinephrine on sympathetic outflow in healthy subjects

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