Effects of clonidine in the isolated rat testicular capsule
The testicular capsule contracts in response to noradrenaline and adrenaline, but the effects of adrenoceptor agonists, as for instance clonidine, had not yet been thoroughly evaluated. The testicular capsule from adult male Wistar rats was isolated and mounted in organ bath and cumulative concentra...
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Veröffentlicht in: | European journal of pharmacology 2014-03, Vol.726, p.16-26 |
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description | The testicular capsule contracts in response to noradrenaline and adrenaline, but the effects of adrenoceptor agonists, as for instance clonidine, had not yet been thoroughly evaluated. The testicular capsule from adult male Wistar rats was isolated and mounted in organ bath and cumulative concentration curves were performed for clonidine and other adrenergic agonists in the absence or presence of α-adrenoceptors antagonists. The order of potency for agonists (pD2) was clonidine=adrenaline>UK 14,304>noradrenaline>phenylephrine>methoxamine. The consecutive curves for clonidine showed desensitization with 3-fold rightward shift and Emax reduction of 40%. The noradrenaline curves were 4.5, 19 and 190-fold less potent after clonidine pretreatment at 10−5, 10−4 or 10−3M for 10min, respectively, added to Emax decrease by about 20%. Clonidine (10−5M for 10min) was unable to alter the noradrenaline curves if the treatment was made in the presence of idazoxan (α2-adrenoceptor antagonist) whereas prazosin (α1-adrenoceptor antagonist) was ineffective. The effect of idazoxan 3×10−7M on noradrenaline curves was decreased by 50% after clonidine pretreatment, as reflected by the concentration ratio of 5.2±1.2 (treated tissue) and 10.1±1.0 (untreated tissue). However, the concentration ratio for prazosin 3×10−8M was unchanged. After phenoxybenzamine (irreversible antagonist of α1-adrenoceptor) pretreatment, the residual noradrenaline contraction was antagonized by idazoxan or prazosin with pKB values of 7.8 and 5.1, respectively. The results indicate the presence of α2-adrenoceptors in testicular capsule. Furthermore, these receptors may be desensitized by clonidine, causing a decreased potency of noradrenaline. |
doi_str_mv | 10.1016/j.ejphar.2014.01.027 |
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The testicular capsule from adult male Wistar rats was isolated and mounted in organ bath and cumulative concentration curves were performed for clonidine and other adrenergic agonists in the absence or presence of α-adrenoceptors antagonists. The order of potency for agonists (pD2) was clonidine=adrenaline>UK 14,304>noradrenaline>phenylephrine>methoxamine. The consecutive curves for clonidine showed desensitization with 3-fold rightward shift and Emax reduction of 40%. The noradrenaline curves were 4.5, 19 and 190-fold less potent after clonidine pretreatment at 10−5, 10−4 or 10−3M for 10min, respectively, added to Emax decrease by about 20%. Clonidine (10−5M for 10min) was unable to alter the noradrenaline curves if the treatment was made in the presence of idazoxan (α2-adrenoceptor antagonist) whereas prazosin (α1-adrenoceptor antagonist) was ineffective. The effect of idazoxan 3×10−7M on noradrenaline curves was decreased by 50% after clonidine pretreatment, as reflected by the concentration ratio of 5.2±1.2 (treated tissue) and 10.1±1.0 (untreated tissue). However, the concentration ratio for prazosin 3×10−8M was unchanged. After phenoxybenzamine (irreversible antagonist of α1-adrenoceptor) pretreatment, the residual noradrenaline contraction was antagonized by idazoxan or prazosin with pKB values of 7.8 and 5.1, respectively. The results indicate the presence of α2-adrenoceptors in testicular capsule. Furthermore, these receptors may be desensitized by clonidine, causing a decreased potency of noradrenaline.</description><identifier>ISSN: 0014-2999</identifier><identifier>EISSN: 1879-0712</identifier><identifier>DOI: 10.1016/j.ejphar.2014.01.027</identifier><identifier>PMID: 24485887</identifier><language>eng</language><publisher>Netherlands: Elsevier B.V</publisher><subject>Adrenergic alpha-2 Receptor Agonists - pharmacology ; Adrenergic Antagonists - pharmacology ; Animals ; Clonidine ; Clonidine - pharmacology ; Desensitization ; Dose-Response Relationship, Drug ; Fertility - physiology ; In Vitro Techniques ; Male ; Muscle Contraction - drug effects ; Muscle, Smooth - drug effects ; Muscle, Smooth - physiology ; Rat testicular capsule ; Rats ; Rats, Wistar ; Testis - drug effects ; Testis - physiology ; α2-Adrenoceptors</subject><ispartof>European journal of pharmacology, 2014-03, Vol.726, p.16-26</ispartof><rights>2014</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c474t-c63452a44798d4901aa8dfaf30de2afd581602c70cb566f1722802b068a95aa73</citedby><cites>FETCH-LOGICAL-c474t-c63452a44798d4901aa8dfaf30de2afd581602c70cb566f1722802b068a95aa73</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0014299914000466$$EHTML$$P50$$Gelsevier$$Hfree_for_read</linktohtml><link.rule.ids>314,776,780,3537,27903,27904,65309</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24485887$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Dantas da Silva Júnior, Edilson</creatorcontrib><creatorcontrib>Palmieri de Souza, Bruno</creatorcontrib><creatorcontrib>Quintella Dantas Rodrigues, Juliano</creatorcontrib><creatorcontrib>Caricati-Neto, Afonso</creatorcontrib><creatorcontrib>Jurkiewicz, Aron</creatorcontrib><creatorcontrib>Jurkiewicz, Neide H.</creatorcontrib><title>Effects of clonidine in the isolated rat testicular capsule</title><title>European journal of pharmacology</title><addtitle>Eur J Pharmacol</addtitle><description>The testicular capsule contracts in response to noradrenaline and adrenaline, but the effects of adrenoceptor agonists, as for instance clonidine, had not yet been thoroughly evaluated. The testicular capsule from adult male Wistar rats was isolated and mounted in organ bath and cumulative concentration curves were performed for clonidine and other adrenergic agonists in the absence or presence of α-adrenoceptors antagonists. The order of potency for agonists (pD2) was clonidine=adrenaline>UK 14,304>noradrenaline>phenylephrine>methoxamine. The consecutive curves for clonidine showed desensitization with 3-fold rightward shift and Emax reduction of 40%. The noradrenaline curves were 4.5, 19 and 190-fold less potent after clonidine pretreatment at 10−5, 10−4 or 10−3M for 10min, respectively, added to Emax decrease by about 20%. Clonidine (10−5M for 10min) was unable to alter the noradrenaline curves if the treatment was made in the presence of idazoxan (α2-adrenoceptor antagonist) whereas prazosin (α1-adrenoceptor antagonist) was ineffective. The effect of idazoxan 3×10−7M on noradrenaline curves was decreased by 50% after clonidine pretreatment, as reflected by the concentration ratio of 5.2±1.2 (treated tissue) and 10.1±1.0 (untreated tissue). However, the concentration ratio for prazosin 3×10−8M was unchanged. After phenoxybenzamine (irreversible antagonist of α1-adrenoceptor) pretreatment, the residual noradrenaline contraction was antagonized by idazoxan or prazosin with pKB values of 7.8 and 5.1, respectively. The results indicate the presence of α2-adrenoceptors in testicular capsule. Furthermore, these receptors may be desensitized by clonidine, causing a decreased potency of noradrenaline.</description><subject>Adrenergic alpha-2 Receptor Agonists - pharmacology</subject><subject>Adrenergic Antagonists - pharmacology</subject><subject>Animals</subject><subject>Clonidine</subject><subject>Clonidine - pharmacology</subject><subject>Desensitization</subject><subject>Dose-Response Relationship, Drug</subject><subject>Fertility - physiology</subject><subject>In Vitro Techniques</subject><subject>Male</subject><subject>Muscle Contraction - drug effects</subject><subject>Muscle, Smooth - drug effects</subject><subject>Muscle, Smooth - physiology</subject><subject>Rat testicular capsule</subject><subject>Rats</subject><subject>Rats, Wistar</subject><subject>Testis - drug effects</subject><subject>Testis - physiology</subject><subject>α2-Adrenoceptors</subject><issn>0014-2999</issn><issn>1879-0712</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kEtLxDAUhYMozjj6D0S6dNN6kyZNiiDIMD5gwI2uQyYPJqXTjkkr-O_N0NGlq7u459xzz4fQNYYCA67umsI2-60KBQFMC8AFEH6C5ljwOgeOySmaQ9rkpK7rGbqIsQEAVhN2jmaEUsGE4HN0v3LO6iFmvct023fe-M5mvsuGbRqxb9VgTRbUkA02Dl6PrQqZVvs4tvYSnTnVRnt1nAv08bR6X77k67fn1-XjOteU0yHXVUkZUZTyWhhaA1ZKGKdcCcYS5QwTuAKiOegNqyqHOSECyAYqoWqmFC8X6Ha6uw_955jekDsftW1b1dl-jBKzktDUhlRJSiepDn2MwTq5D36nwrfEIA_YZCMnbPKATQKWCVuy3RwTxs3Omj_TL6ckeJgENvX88jbIqL3ttDU-JHzS9P7_hB80_n7y</recordid><startdate>20140305</startdate><enddate>20140305</enddate><creator>Dantas da Silva Júnior, Edilson</creator><creator>Palmieri de Souza, Bruno</creator><creator>Quintella Dantas Rodrigues, Juliano</creator><creator>Caricati-Neto, Afonso</creator><creator>Jurkiewicz, Aron</creator><creator>Jurkiewicz, Neide H.</creator><general>Elsevier B.V</general><scope>6I.</scope><scope>AAFTH</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>20140305</creationdate><title>Effects of clonidine in the isolated rat testicular capsule</title><author>Dantas da Silva Júnior, Edilson ; Palmieri de Souza, Bruno ; Quintella Dantas Rodrigues, Juliano ; Caricati-Neto, Afonso ; Jurkiewicz, Aron ; Jurkiewicz, Neide H.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c474t-c63452a44798d4901aa8dfaf30de2afd581602c70cb566f1722802b068a95aa73</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Adrenergic alpha-2 Receptor Agonists - pharmacology</topic><topic>Adrenergic Antagonists - pharmacology</topic><topic>Animals</topic><topic>Clonidine</topic><topic>Clonidine - pharmacology</topic><topic>Desensitization</topic><topic>Dose-Response Relationship, Drug</topic><topic>Fertility - physiology</topic><topic>In Vitro Techniques</topic><topic>Male</topic><topic>Muscle Contraction - drug effects</topic><topic>Muscle, Smooth - drug effects</topic><topic>Muscle, Smooth - physiology</topic><topic>Rat testicular capsule</topic><topic>Rats</topic><topic>Rats, Wistar</topic><topic>Testis - drug effects</topic><topic>Testis - physiology</topic><topic>α2-Adrenoceptors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Dantas da Silva Júnior, Edilson</creatorcontrib><creatorcontrib>Palmieri de Souza, Bruno</creatorcontrib><creatorcontrib>Quintella Dantas Rodrigues, Juliano</creatorcontrib><creatorcontrib>Caricati-Neto, Afonso</creatorcontrib><creatorcontrib>Jurkiewicz, Aron</creatorcontrib><creatorcontrib>Jurkiewicz, Neide H.</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>European journal of pharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Dantas da Silva Júnior, Edilson</au><au>Palmieri de Souza, Bruno</au><au>Quintella Dantas Rodrigues, Juliano</au><au>Caricati-Neto, Afonso</au><au>Jurkiewicz, Aron</au><au>Jurkiewicz, Neide H.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Effects of clonidine in the isolated rat testicular capsule</atitle><jtitle>European journal of pharmacology</jtitle><addtitle>Eur J Pharmacol</addtitle><date>2014-03-05</date><risdate>2014</risdate><volume>726</volume><spage>16</spage><epage>26</epage><pages>16-26</pages><issn>0014-2999</issn><eissn>1879-0712</eissn><abstract>The testicular capsule contracts in response to noradrenaline and adrenaline, but the effects of adrenoceptor agonists, as for instance clonidine, had not yet been thoroughly evaluated. The testicular capsule from adult male Wistar rats was isolated and mounted in organ bath and cumulative concentration curves were performed for clonidine and other adrenergic agonists in the absence or presence of α-adrenoceptors antagonists. The order of potency for agonists (pD2) was clonidine=adrenaline>UK 14,304>noradrenaline>phenylephrine>methoxamine. The consecutive curves for clonidine showed desensitization with 3-fold rightward shift and Emax reduction of 40%. The noradrenaline curves were 4.5, 19 and 190-fold less potent after clonidine pretreatment at 10−5, 10−4 or 10−3M for 10min, respectively, added to Emax decrease by about 20%. Clonidine (10−5M for 10min) was unable to alter the noradrenaline curves if the treatment was made in the presence of idazoxan (α2-adrenoceptor antagonist) whereas prazosin (α1-adrenoceptor antagonist) was ineffective. The effect of idazoxan 3×10−7M on noradrenaline curves was decreased by 50% after clonidine pretreatment, as reflected by the concentration ratio of 5.2±1.2 (treated tissue) and 10.1±1.0 (untreated tissue). However, the concentration ratio for prazosin 3×10−8M was unchanged. After phenoxybenzamine (irreversible antagonist of α1-adrenoceptor) pretreatment, the residual noradrenaline contraction was antagonized by idazoxan or prazosin with pKB values of 7.8 and 5.1, respectively. The results indicate the presence of α2-adrenoceptors in testicular capsule. Furthermore, these receptors may be desensitized by clonidine, causing a decreased potency of noradrenaline.</abstract><cop>Netherlands</cop><pub>Elsevier B.V</pub><pmid>24485887</pmid><doi>10.1016/j.ejphar.2014.01.027</doi><tpages>11</tpages><oa>free_for_read</oa></addata></record> |
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subjects | Adrenergic alpha-2 Receptor Agonists - pharmacology Adrenergic Antagonists - pharmacology Animals Clonidine Clonidine - pharmacology Desensitization Dose-Response Relationship, Drug Fertility - physiology In Vitro Techniques Male Muscle Contraction - drug effects Muscle, Smooth - drug effects Muscle, Smooth - physiology Rat testicular capsule Rats Rats, Wistar Testis - drug effects Testis - physiology α2-Adrenoceptors |
title | Effects of clonidine in the isolated rat testicular capsule |
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