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Article: The mechanisms of enhancement and inhibition of field stimulation responses of guinea-pig vas deferens by prostacyclin analogues

TitleThe mechanisms of enhancement and inhibition of field stimulation responses of guinea-pig vas deferens by prostacyclin analogues
Authors
KeywordsCicaprost
EP 3-receptors
Guinea-pig vas deferens
K +-channel blockers
Noradrenaline release
P(2X)-receptors
Prostacyclin analogues
Prostanoid IP-receptors
Tetrodotoxin
Issue Date1997
PublisherJohn Wiley & Sons Ltd. The Journal's web site is located at http://www.wiley.com/bw/journal.asp?ref=0007-1188&site=1
Citation
British Journal of Pharmacology, 1997, v. 121 n. 7, p. 1413-1421 How to Cite?
Abstract1. In the guinea-pig isolated vas deferens preparation bathed in Tyrode's solution, the prostacyclin analogues, cicaprost, TEI-9063, iloprost, taprostene and benzodioxane-prostacyclin, enhanced twitch responses to submaximal electrical field stimulation (20%-EFS). The high potency of cicaprost (EC 150 = 1.3 nM) and the relative potencies of the analogues (equi-effective molar ratios = 1.0, 0.85, 1.6, 17 and 82, respectively) suggest the involvement of a prostacyclin (IP-) receptor. 2. Maximum enhancement induced by cicaprost in 2.5 mM K + Krebs-Henseleit solution was similar to that in Tyrode solution (2.7 mM K+), but was progressively reduced as the K+ concentration was increased to 3.9, 5.9 and 11.9 mM. There was also a greater tendency for the other prostacyclin analogues to inhibit EFS responses in 5.9 mM standard K + Krebs-Henseleit solution; this may be attributed to their agonist actions on presynaptic EP 3-receptors resulting in inhibition of transmitter release. 3. The EFS enhancing action of cicaprost was not affected by the α 1-adrenoceptor antagonist prazosin (100 and 1000 nM). Cicaprost (20 and 200 nM) did not affect contractile responses of the vas deferens to either ATP (5 μM) or α,β-methylene ATP (1 μM) in the presence of tetrodotoxin (TTX, 100 nM). In addition, enhancement by cicaprost of responses to higher concentrations of ATP (30 and 300 μM) in the absence of TTX, as shown previously by others, was not seen. Prostaglandin E 2 (PGE 2, 10 nM) and another prostacyclin analogue TEI-3356 (20 nM) enhanced purinoceptor agonist responses. Unexpectedly, TTX (0.1 and 1 μM) partially inhibited contractions elicited by 10-1000 μM ATP; contractions elicited by 1-3 μM ATP were unaffected. Further studies are required to establish whether a pre- or post-synaptic mechanism is involved. 4. In a separate series of experiments, cicaprost (5-250 nM), TEI-9063 (3-300 nM), 4-aminopyridine (10-100 μM) and tetraethylammonium (100-1000 μM) enhanced both 20%-EFS responses and the accompanying overflow of noradrenaline to a similar extent. In further experiments with the EP 1-receptor antagonist AH 6809, TEI-3356 (1.0-100 nM) and the EP 3-receptor agonist, sulprostone (0.1-1.0 nM) inhibited both maximal EFS responses and noradrenaline overflow, thus confirming previous reports of the high activity of TEI-3356 at the EP 3-receptor. Cicaprost had no significant effect on noradrenaline overflow at 10 and 100 nM, but produced a modest inhibition at 640 nM. 5. In conclusion, our studies show that prostacyclin analogues (particularly TEI-3356) can inhibit EFS responses of the guinea-pig vas deferens by acting as agonists at presynaptic EP 3-receptors. Prostacyclin analogues (particularly cicaprost and TEI-9063) can also enhance EFS responses through activation of IP-receptors. The mechanism of the enhancement has not been rigorously established but from our results we favour a presynaptic action to increase transmitter release.
Persistent Identifierhttp://hdl.handle.net/10722/49291
ISSN
2023 Impact Factor: 6.8
2023 SCImago Journal Rankings: 2.119
PubMed Central ID
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorTam, FSFen_HK
dc.contributor.authorChan, KMen_HK
dc.contributor.authorBourreau, JPen_HK
dc.contributor.authorJones, RLen_HK
dc.date.accessioned2008-06-12T06:38:39Z-
dc.date.available2008-06-12T06:38:39Z-
dc.date.issued1997en_HK
dc.identifier.citationBritish Journal of Pharmacology, 1997, v. 121 n. 7, p. 1413-1421en_HK
dc.identifier.issn0007-1188en_HK
dc.identifier.urihttp://hdl.handle.net/10722/49291-
dc.description.abstract1. In the guinea-pig isolated vas deferens preparation bathed in Tyrode's solution, the prostacyclin analogues, cicaprost, TEI-9063, iloprost, taprostene and benzodioxane-prostacyclin, enhanced twitch responses to submaximal electrical field stimulation (20%-EFS). The high potency of cicaprost (EC 150 = 1.3 nM) and the relative potencies of the analogues (equi-effective molar ratios = 1.0, 0.85, 1.6, 17 and 82, respectively) suggest the involvement of a prostacyclin (IP-) receptor. 2. Maximum enhancement induced by cicaprost in 2.5 mM K + Krebs-Henseleit solution was similar to that in Tyrode solution (2.7 mM K+), but was progressively reduced as the K+ concentration was increased to 3.9, 5.9 and 11.9 mM. There was also a greater tendency for the other prostacyclin analogues to inhibit EFS responses in 5.9 mM standard K + Krebs-Henseleit solution; this may be attributed to their agonist actions on presynaptic EP 3-receptors resulting in inhibition of transmitter release. 3. The EFS enhancing action of cicaprost was not affected by the α 1-adrenoceptor antagonist prazosin (100 and 1000 nM). Cicaprost (20 and 200 nM) did not affect contractile responses of the vas deferens to either ATP (5 μM) or α,β-methylene ATP (1 μM) in the presence of tetrodotoxin (TTX, 100 nM). In addition, enhancement by cicaprost of responses to higher concentrations of ATP (30 and 300 μM) in the absence of TTX, as shown previously by others, was not seen. Prostaglandin E 2 (PGE 2, 10 nM) and another prostacyclin analogue TEI-3356 (20 nM) enhanced purinoceptor agonist responses. Unexpectedly, TTX (0.1 and 1 μM) partially inhibited contractions elicited by 10-1000 μM ATP; contractions elicited by 1-3 μM ATP were unaffected. Further studies are required to establish whether a pre- or post-synaptic mechanism is involved. 4. In a separate series of experiments, cicaprost (5-250 nM), TEI-9063 (3-300 nM), 4-aminopyridine (10-100 μM) and tetraethylammonium (100-1000 μM) enhanced both 20%-EFS responses and the accompanying overflow of noradrenaline to a similar extent. In further experiments with the EP 1-receptor antagonist AH 6809, TEI-3356 (1.0-100 nM) and the EP 3-receptor agonist, sulprostone (0.1-1.0 nM) inhibited both maximal EFS responses and noradrenaline overflow, thus confirming previous reports of the high activity of TEI-3356 at the EP 3-receptor. Cicaprost had no significant effect on noradrenaline overflow at 10 and 100 nM, but produced a modest inhibition at 640 nM. 5. In conclusion, our studies show that prostacyclin analogues (particularly TEI-3356) can inhibit EFS responses of the guinea-pig vas deferens by acting as agonists at presynaptic EP 3-receptors. Prostacyclin analogues (particularly cicaprost and TEI-9063) can also enhance EFS responses through activation of IP-receptors. The mechanism of the enhancement has not been rigorously established but from our results we favour a presynaptic action to increase transmitter release.en_HK
dc.format.extent418 bytes-
dc.format.mimetypetext/html-
dc.languageengen_HK
dc.publisherJohn Wiley & Sons Ltd. The Journal's web site is located at http://www.wiley.com/bw/journal.asp?ref=0007-1188&site=1en_HK
dc.relation.ispartofBritish Journal of Pharmacologyen_HK
dc.subjectCicaprosten_HK
dc.subjectEP 3-receptorsen_HK
dc.subjectGuinea-pig vas deferensen_HK
dc.subjectK +-channel blockersen_HK
dc.subjectNoradrenaline releaseen_HK
dc.subjectP(2X)-receptorsen_HK
dc.subjectProstacyclin analoguesen_HK
dc.subjectProstanoid IP-receptorsen_HK
dc.subjectTetrodotoxinen_HK
dc.titleThe mechanisms of enhancement and inhibition of field stimulation responses of guinea-pig vas deferens by prostacyclin analoguesen_HK
dc.typeArticleen_HK
dc.identifier.emailBourreau, JP: bourreau@hkucc.hku.hken_HK
dc.identifier.authorityBourreau, JP=rp00389en_HK
dc.description.naturelink_to_OA_fulltexten_HK
dc.identifier.doi10.1038/sj.bjp.0701275en_HK
dc.identifier.pmid9257922-
dc.identifier.pmcidPMC1564834-
dc.identifier.scopuseid_2-s2.0-0030757858en_HK
dc.identifier.hkuros45519-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-0030757858&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume121en_HK
dc.identifier.issue7en_HK
dc.identifier.spage1413en_HK
dc.identifier.epage1421en_HK
dc.identifier.isiWOS:A1997XN08600024-
dc.publisher.placeUnited Kingdomen_HK
dc.identifier.scopusauthoridTam, FSF=35977798800en_HK
dc.identifier.scopusauthoridChan, KM=7406033476en_HK
dc.identifier.scopusauthoridBourreau, JP=7003927886en_HK
dc.identifier.scopusauthoridJones, RL=7501543251en_HK
dc.identifier.issnl0007-1188-

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