Post‐natal development of functional neurotransmission in rat vas deferens

Macdonald, Angus; McGrath, J.C.

doi:10.1111/j.1476-5381.1984.tb16438.x

Cited by 35 publications

(11 citation statements)

References 21 publications

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“…The responses to NA showed a different pattern of development and decreased with age, and this suggests that in the neonatal tissue, ATP is more important as a transmitter than is NA. These results are in agreement with those of MacDonald & McGrath (1984), who showed that the vasa deferentia from sexually immature rats (3-4 weeks old) were more sensitive to NA than were the vasa from adult rats, but appeared to lack functional adrenergic transmission. Some workers have been able to distinguish a first non-adrenergic (purinergic) phase of the contractile response from a second adrenergic phase (McGrath, 1978;Amobi & Smith, 1987), although others (Major et al, 1989) have concluded that both co-transmitters contribute to each phase.…”

Section: Discussionsupporting

confidence: 92%

Characterization and ontogeny of P1‐purinoceptors on rat vas deferens

Hourani

Nicholls

Lee

et al. 1993

British J Pharmacology

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1 The PI-purinoceptors which mediate the inhibition by adenosine of nerve-mediated contraction of the rat vas deferens have been investigated by use of the agonists N6-cyclopentyladenosine (CPA) and 5'-N-ethylcarboxamidoadenosine (NECA) and the Al-selective antagonist 1,3-dipropyl-8-cyclopentylxanthine (DPCPX). The ontogeny of the responses to adenosine and to the two co-transmitters which induce the contractions in this tissue, adenosine 5'-triphosphate (ATP) and noradrenaline (NA), have also been studied. 2 The order of potency for the adenosine agonists in inhibiting the nerve-mediated contractions was CPA = NECA> adenosine. Micromolar concentrations of DPCPX were required to antagonize the inhibition by adenosine and NECA of nerve-mediated responses, whereas the inhibitory effect of CPA was antagonized by nanomolar concentrations of the antagonist. 3 NECA and adenosine inhibited contractions induced by ATP (1OIM) or by NA (1OIM), NECA being at least ten fold more potent than adenosine, whereas CPA was inactive. Micromolar concentrations of DPCPX were required to antagonize the effect of adenosine on the contractions induced by ATP (1OIM). 4 Nerve-stimulated contractions could be observed in neonatal tissues from day 15 and increased with age, and could be inhibited by adenosine from this time, the potency of adenosine decreasing with age. Responses to ATP also appeared at day 15 and increased with age up to day 25, while responses to NA were present from day 10 (the earliest day tested) and decreased with age.5 These results show that the rat vas deferens contains both prejunctional Al-receptors and postjunctional A2-receptors, and that adenosine acts on the latter populations to inhibit nerve-mediated contractions. The high potency of adenosine in the neonate and the parallel development of responses to ATP and to nerve-mediated contractions support suggestions that purinergic responses may be particularly important in neonatal tissues.

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Section: Discussionsupporting

confidence: 92%

Characterization and ontogeny of P1‐purinoceptors on rat vas deferens

Hourani

Nicholls

Lee

et al. 1993

British J Pharmacology

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“…EJPs produced by ATP in response to sympathetic nerve stimulation of the vas deferens were not observed in mice less than 18 days postnatal [272]. At 3 weeks postnatal (the earliest time studied), the responses of the rat vas deferens to field stimulation with single or trains of pulses lacked the adrenergic component, but the non-adrenergic component was present [273]. Responses to ATP first appeared at day 15 and then increased with age [264].…”

Section: Vas Deferensmentioning

confidence: 98%

Purinergic signalling during development and ageing

Burnstock

Dale

2015

Purinergic Signalling

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Extracellular purines and pyrimidines play major roles during embryogenesis, organogenesis, postnatal development and ageing in vertebrates, including humans. Pluripotent stem cells can differentiate into three primary germ layers of the embryo but may also be involved in plasticity and repair of the adult brain. These cells express the molecular components necessary for purinergic signalling, and their developmental fates can be manipulated via this signalling pathway. Functional P1, P2Y and P2X receptor subtypes and ectonucleotidases are involved in the development of different organ systems, including heart, blood vessels, skeletal muscle, urinary bladder, central and peripheral neurons, retina, inner ear, gut, lung and vas deferens. The importance of purinergic signalling in the ageing process is suggested by changes in expression of A1 and A2 receptors in old rat brains and reduction of P2X receptor expression in ageing mouse brain. By contrast, in the periphery, increases in expression of P2X3 and P2X4 receptors are seen in bladder and pancreas.

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“…Changes in various aspects of ␣ 1 -adrenergic neurotransmission associated with age have been reported (21)(22)(23), so potential age-related differences in the inhibitory action of -TIA were examined. This was investigated in dissociated cells only, because the contractile response of the juvenile rat vas deferens is quite weak (24).…”

Section: Discussionmentioning

confidence: 99%

Allosteric α1-Adrenoreceptor Antagonism by the Conopeptide ρ-TIA

Sharpe

Thomas

Loughnan

et al. 2003

Journal of Biological Chemistry

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A peptide contained in the venom of the predatory marine snail Conus tulipa, -TIA, has previously been shown to possess ␣ 1 -adrenoreceptor antagonist activity. Here, we further characterize its pharmacological activity as well as its structure-activity relationships. In the isolated rat vas deferens, -TIA inhibited ␣ 1 -adrenoreceptor-mediated increases in cytosolic Ca 2؉ concentration that were triggered by norepinephrine, but did not affect presynaptic ␣ 2 -adrenoreceptor-mediated responses. In radioligand binding assays using [125 I]HEAT, -TIA displayed slightly greater potency at the ␣ 1B than at the ␣ 1A or ␣ 1D subtypes. Moreover, although it did not affect the rate of association for [ 3 H]prazosin binding to the ␣ 1B -adrenoreceptor, the dissociation rate was increased, indicating non-competitive antagonism by -TIA. N-terminally truncated analogs of -TIA were less active than the full-length peptide, with a large decline in activity observed upon removal of the fourth residue of -TIA (Arg 4 ). An alanine walk of -TIA confirmed the importance of Arg 4 for activity and revealed a number of other residues clustered around Arg 4 that contribute to the potency of -TIA. The unique allosteric antagonism of -TIA resulting from its interaction with receptor residues that constitute a binding site that is distinct from that of the classical competitive ␣ 1 -adrenoreceptor antagonists may allow the development of inhibitors that are highly subtype selective.␣ 1 -Adrenoceptors, members of the G protein-coupled receptor superfamily, are the predominant mediators of the response to norepinephrine released from the sympathetic nerves that innervate resistance vessels (1). Norepinephrine release modulates vascular tone and, as such, ␣ 1 -adrenoreceptors are critically involved in circulatory homeostasis. Several ␣ 1 -adrenoreceptor antagonists, such as the quinazoline derivative, prazosin, are widely used for the treatment of hypertension. ␣ 1 -Adrenoreceptor antagonists are also used to treat bladder outlet obstruction in benign prostatic hyperplasia (for review, see Ref.2) because of their ability to relax smooth muscle.Nevertheless, the ␣ 1 -adrenoreceptor ligands developed to date interact largely with residues of the transmembrane segments that are homologous between the various receptor subtypes, rather than with residues forming the framework regions (the intra-and extracellular loops). It is not surprising, therefore, that available agonists, and also antagonists, show limited subtype selectivity (affinities differing by 50-fold or less between the various subtypes). For this reason, we sought to identify novel ligands that are likely to interact allosterically and, thus, more likely with the framework residues that are distinct between the three ␣ 1 -adrenoreceptor subtypes (␣ 1A , ␣ 1B , and ␣ 1D ).The venoms of cone snails (marine gastropods of the genus Conus) contain bioactive peptides that disrupt neurotransmission. These compounds are referred to generically as "conopeptides" or "conotoxins." Individual ...

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Post‐natal development of functional neurotransmission in rat vas deferens

Cited by 35 publications

References 21 publications

Characterization and ontogeny of P1‐purinoceptors on rat vas deferens

Characterization and ontogeny of P1‐purinoceptors on rat vas deferens

Purinergic signalling during development and ageing

Allosteric α1-Adrenoreceptor Antagonism by the Conopeptide ρ-TIA

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