Post‐natal Change and Regional Variation of the Response of the Vas Deferens of New‐born Rats to Autonomic Drugs

Chiu‐Wei, Yen‐Fun; Kasuya, Yutaka; Watanabe, Minoru

doi:10.1113/expphysiol.1984.sp002862

Cited by 3 publications

(7 citation statements)

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“…As described in our preceding paper (Chiu-Wei et al 1984), up to about 3 weeks after birth many agonists could produce a maximum contraction comparable to the full contractility in both halves, but thereafter the drug-induced contractile response showed a marked regional variation and the maximum responses to some agonists became progressively smaller than the contraction induced by 150 mm potassium Krebs-Ringer, which was regarded as an approximate measure of the full contractility of a preparation.…”

Section: Discussionmentioning

confidence: 99%

“…We tentatively called this phenomenon a 'retrogression relative to full contractility' (Chiu-Wei et al 1984). It is possible that this phenomenon is one of the causes of the increased maximum contractility in response to agonists after denervation, and if it is assumed that the cause of retrogression was removed by denervation, though there is no available evidence at present, the mechanisms underlying the denervation supersensitivity could be understood.…”

Section: Discussionmentioning

confidence: 99%

“…In the preceding paper (Chiu-Wei et al 1984) the response of the prostatic half to most of the agonists (NA, isoprenaline, tyramine and MCh) reached plateau with age at levels much lower than the corresponding response of the epididymal half, with the exception of those to TMA and ACh. We tentatively called this phenomenon a 'retrogression relative to full contractility' (Chiu-Wei et al 1984).…”

Section: Discussionmentioning

confidence: 99%

“…In the preceding study we examined (Chiu-Wei, Kasuya & Watanabe, 1984) the post-natal development of pharmacological characteristics of the rat vas deferens, and found different developmental courses between epididymal and prostatic halves of the vas. Contractility of both halves increased in parallel with organ weight, but the maximum contractile responses to adrenergic and cholinergic agents of the two halves showed different courses of development.…”

Section: Introductionmentioning

confidence: 99%

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Post‐natal Change in the Effect of Denervation on the Rat Vas Deferens

1984

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SUMMARYThe vas deferens of 14-54 d old rats was denervated, isolated after 7 d, divided into prostatic and epididymal halves, and denervation supersensitivity to noradrenaline, acetylcholine, methacholine and tetramethylammonium (TMA) was examined. The supersensitivity to any of these agonists did not appear in rats younger than 21 d of age. Thereafter a leftward shift of the dose-response curve and an increase in the maximum contraction to noradrenaline were observed. The maximum contraction became progressively greater with development in the prostatic half but was approximately constant in the epididymal half. Supersensitivity to methacholine distinctly developed with age in the epididymal half. Only a subsensitivity to TMA was observed, suggesting that TMA acts on the nerve. The effect of denervation on the response to acetylcholine in the epididymal half resembled that to methacholine, and in the prostatic half resembled that to TMA. The developmental change in the effect of denervation on noradrenaline was discussed in relation to the full contractile ability of the vas halves, and that to cholinergic drugs was discussed in relation to nicotinic and muscarinic receptor population.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Post‐natal Change in the Effect of Denervation on the Rat Vas Deferens

1984

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“…This was investigated in dissociated cells only, because the contractile response of the juvenile rat vas deferens is quite weak (24). -TIA was ϳ3.5 times more potent at inhibiting Ca 2ϩ spikes following ␣ 1 -adrenoreceptor activation by norepinephrine in cells from adult rats compared with those taken from juvenile rats.…”

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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Vas deferens – A model used to establish sympathetic cotransmission

Burnstock

Verkhratsky

2010

Trends in Pharmacological Sciences

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Post‐natal Change and Regional Variation of the Response of the Vas Deferens of New‐born Rats to Autonomic Drugs

Cited by 3 publications

References 7 publications

Post‐natal Change in the Effect of Denervation on the Rat Vas Deferens

Post‐natal Change in the Effect of Denervation on the Rat Vas Deferens

Allosteric α1-Adrenoreceptor Antagonism by the Conopeptide ρ-TIA

Vas deferens – A model used to establish sympathetic cotransmission

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