An investigation of presynaptic α‐adrenoceptor subtypes in the pithed rat heart

Docherty, James R.

doi:10.1111/j.1476-5381.1983.tb09416.x

Cited by 50 publications

(13 citation statements)

References 9 publications

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“…The reduced sensitivity to yohimbine in the present study suggests a similarity of the receptor to the M2D subtype (Simonneaux et al, 1991;Limberger et al, 1992). Alternatively, the results may suggest the involvement of more than one x-adrenoceptor subtype as has been previously postulated (Docherty, 1983;Hicks et al, 1986;Daly et al, 1988;Kawasaki et al, 1989;Murphy & Majewski, 1989;Harsing & Vizi, 1991;Wilson & Minneman, 1991;Rump et al, 1992).…”

Section: Effects Ofpertussis Toxin On Inhibition Of K+-evoked Overflocontrasting

confidence: 48%

Involvement of pertussis toxin‐sensitive and ‐insensitive mechanisms in α‐adrenoceptor modulation of noradrenaline release from rat sympathetic neurones in tissue culture

Hill

Powis

Hendry

1993

British J Pharmacology

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1 Sympathetic neurones derived from superior cervical ganglia of neonatal rats and maintained in tissue culture were used to investigate the modulation of neurotransmitter release by presynaptic receptors. Three week old cultures of neurones were loaded with [3H]-noradrenaline to label endogenous neurotransmitter stores. Release of noradrenaline was evoked by depolarization with raised extracellular K+ in the presence of desipramine and corticosterone to prevent uptake of released catecholamine. 2 Potassium (55 mmol 1-) depolarization for 30 s caused more than a four fold increase in 3H overflow from basal levels but this increase was reduced by up to 40% in the presence of exogenous noradrenaline (1 timol 1`). The inhibition by noradrenaline of depolarization-evoked overflow was blocked by the aI/a2-adrenoceptor antagonist, phentolamine. Phentolamine alone did not increase K+-evoked 3H overflow. 3 The a2-adrenoceptor antagonist, yohimbine, produced a concentration-dependent block of the inhibition by noradrenaline of K+-evoked overflow, while the ax-adrenoceptor antagonist, prazosin, was without effect at concentrations up to 0.1 Lmol 1'. 4 The P-adrenoceptor antagonist, propranolol, neither reduced K+-evoked overflow nor increased the degree of inhibition caused by the addition of 1 1tmol 1' noradrenaline.5 The M2-adrenoceptor agonist, clonidine (I iLmol 11) was less effective than noradrenaline at inhibiting K+-evoked overflow, while the a,-adrenoceptor agonist, phenylephrine (1,umol 1I) had no significant effect.6 The L-channel calcium blocker, nicardipine (1 timol 1-') significantly inhibited 3H overflow evoked by K+. In the presence of L-channel block, however, noradrenaline still inhibited residual evoked overflow. 7 In the presence or absence of nicardipine, pertussis toxin pretreatment (1 nmol 1-') reduced, but did not prevent, the effect of noradrenaline (1 tLmol 1'). Pertussis toxin alone caused a significant enhancement of K+-evoked 3H overflow. 8 The data indicate that on postganglionic neurones of cultured rat sympathetic ganglia there are M2-adrenoceptors that modulate neurotransmitter release, but no functional P-adrenoceptors that mediate an enhancement of transmitter release. The data suggest further that in this preparation the mechanism of a2-adrenoceptor modulation may involve pertussis toxin sensitive and insensitive G-proteins and effects on calcium channels other than L-type.

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Section: Effects Ofpertussis Toxin On Inhibition Of K+-evoked Overflocontrasting

confidence: 48%

Involvement of pertussis toxin‐sensitive and ‐insensitive mechanisms in α‐adrenoceptor modulation of noradrenaline release from rat sympathetic neurones in tissue culture

Hill

Powis

Hendry

1993

British J Pharmacology

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“…Therefore, the low apparent pK B of 7.43 for prazosin against phenylephrine implies the involvement of mixed pre-and post-synaptic α-adrenoceptors in the action of phenylephrine in the response to transmural stimulation. Since there is evidence for the presence of α 1 -adrenoceptors at pre-synaptic sites in the cardiac muscle and guinea-pig vas deferens (Docherty 1983, Ellis et al 1990), the involvement of presynaptic α 1 -adrenoceptors in modulation of rat intestinal motility can not be excluded by present study. However, the rank orders and relative potencies of agonists indicates that the predominant α-adrenoceptors of cholinergic neurones supplying the circular muscle are of α 2 kind.…”

Section: Discussionmentioning

confidence: 82%

Characterisation of pre- and post-synaptic α-adrenoceptors in modulation of the rat ileum longitudinal and circular muscle activities

Liu

Coupar

1997

Naunyn-Schmiedeberg's Arch Pharmacol

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Previous study has shown that alpha2D-adrenoceptors are involved in modulation of peristalsis in the rat ileum. The aim of the present study was to determine the tissue location of alpha-adrenoceptors in the rat ileum by using a recently devised method. The pre-synaptic alpha-adrenoceptors were characterised by measuring the potencies of agonists to inhibit transmurally-evoked (1 ms pulses, 10 Hz, 8-10 s trains) contractions of the longitudinal and circular muscles and the affinities of antagonists. Post synaptic alpha-adrenoceptors were identified by screening agonists and antagonists in carbachol-contracted tissues. In the circular muscle the order of potencies for inhibiting transmurally-induced contraction was: clonidine > or = oxymetazoline > or = UK 14,304 > or = guanfacine > talipexole > phenylephrine > azepexole. The potency ratios relative to clonidine correlated to those previously derived using the rat ileum peristaltic reflex preparation. Most of the alpha-adrenoceptor agonists, however, caused only small inhibitions of the longitudinal muscle contraction in response to transmural stimulation, except phenylephrine and azepexole. RX 821002, yohimbine, rauwolscine, BRL 44408, phentolamine, idazoxan, ARC 239, and prazosin inhibited the effect of clonidine on the circular muscle response with apparent pK(B) values best correlated with pK(B) or pKi values derived from the rat ileum peristaltic reflex preparation and other tissues known to have the alpha2D-subtype. The rank order of potencies at inhibiting carbachol-induced responses of both muscle layers was: phenylephrine > or = oxymetazoline > clonidine > or = talipexole > azepexole >> guanfacine. UK 14,304 was inactive up to 10 microM. The EC50 value of each agonist on the longitudinal muscle was not significantly different to the corresponding value on the circular muscle. Prazosin was more potent than yohimbine at inhibiting the relaxant effect of phenylephrine in both muscle layers of carbachol-contracted tissues. It is concluded that the recently identified alpha2D-adrenoceptors of the rat ileum are located on cholinergic neurons controlling circular muscle contraction. The study also demonstrated the presence of postsynaptic alpha1-adrenoceptors involved in mediating relaxation in both muscle layers.

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“…Again, the effect of phenylephrine was antagonized by prazosin, although less efficiently than by yohimbine. Thus, as well as in the cardiac adrenergic terminals of several animal species (Kobinger & Pichler, 1980;Docherty, 1983;Ledda & Mantelli, 1984 (Neylon & Summers, 1985;Harrison et al, 1991) including those of rat submandibular gland tissue slices and rat brain slices (Turner et al, 1984;Nasseri & Minneman 1987 . Only the effect of the imidazolines however is completely antagonized by M2-blockers, while noradrenaline shows a 'remaining effect' which is insensitive to a(X-, a2-or P-adrenoceptor blockers (Bond et al, 1986a;b).…”

Section: Discussionmentioning

confidence: 99%

α.‐Adrenoceptor modulation of the efferent function of capsaicin‐sensitive sensory neurones in guinea‐pig isolated atria

Amerini

Rubino

Mantelli

et al. 1992

British J Pharmacology

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1 Transmural nerve stimulation of guinea-pig atria, obtained from animals pretreated with reserpine (5 mg kg-', i.p.), in the presence of atropine 1 JAM and of the 13-adrenoceptor blocker CGP 20712A 1 JAM, induced a positive inotropic effect which was reduced by the calcitonin gene-related peptide (CGRP) antagonist hCGRP-(8-37) and abolished by pretreatment with capsaicin 1 JM.2 Noradrenaline concentration-dependently (0.01-10 JAM) reduced the increase in cardiac contractility induced by transmural nerve stimulation. The inhibitory effect of noradrenaline was antagonized by yohimbine (0.5-1 JM), in a dose-dependent manner. Prazosin (0.5-1 JAM) antagonized the effect of noradrenaline and this effect was independent of concentration. 3 In the presence of yohimbine, the lower part of the inhibitory-response curve for noradrenaline was slightly but significantly shifted by prazosin. A similar degree of antagonism was observed in the presence of 1 JAM phenoxybenzamine. 4 The selective X2 agonists BHT 920 and clonidine reduced, in the same concentration-range (0.01-1 JAM), the cardiac response to transmural nerve stimulation in a yohimbine-sensitive fashion.5 Phenylephrine (0.1-100 JAM) and methoxamine (1-300 JAM) also induced an inhibitory effect on transmural nerve stimulation. The effect of phenylephrine was antagonized by yohimbine (1 JM) more efficiently than by prazosin (0.5 JM). 6 These results are in keeping with the presence of inhibitory prejunctional a2-adrenoceptors on cardiac sensory nerve endings which modulate the efferent function of capsaicin-sensitive neurones.

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An investigation of presynaptic α‐adrenoceptor subtypes in the pithed rat heart

Cited by 50 publications

References 9 publications

Involvement of pertussis toxin‐sensitive and ‐insensitive mechanisms in α‐adrenoceptor modulation of noradrenaline release from rat sympathetic neurones in tissue culture

Involvement of pertussis toxin‐sensitive and ‐insensitive mechanisms in α‐adrenoceptor modulation of noradrenaline release from rat sympathetic neurones in tissue culture

Characterisation of pre- and post-synaptic α-adrenoceptors in modulation of the rat ileum longitudinal and circular muscle activities

α.‐Adrenoceptor modulation of the efferent function of capsaicin‐sensitive sensory neurones in guinea‐pig isolated atria

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