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Loss of 5-hydroxytryptamine from mammalian circulating labelled platelets

1. Platelets were obtained from three species of animal: rats, rabbits and dogs. They were labelled with 111 In oxine to tag individual platelets and with 14 C-labelled 5-hydroxytryptamine (5-HT). Doubly labelled platelets from rabbits and dogs were returned to their donors; in the case of rats the...

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Published in:The Journal of physiology 1983-07, Vol.340 (1), p.77-90
Main Authors: Osim, E. E., Wyllie, J. H.
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description 1. Platelets were obtained from three species of animal: rats, rabbits and dogs. They were labelled with 111 In oxine to tag individual platelets and with 14 C-labelled 5-hydroxytryptamine (5-HT). Doubly labelled platelets from rabbits and dogs were returned to their donors; in the case of rats the platelets were injected intravenously into other, identical rats. At time intervals from 2 to 64 hr, blood samples were drawn and platelets were collected. 111 In and 14 C were separately counted. In some experiments animals received the 5-HT precursor, 5-hydroxytryptophan (5-HTP) I.P. (for rats and rabbits) or subcutaneously (for dogs) in a dose of 20 mg/kg daily to accelerate synthesis of 5-HT. 2. 111 In disappeared in approximately an exponential fashion in all experiments and the rate of disappearance was not affected by treatment with 5-HTP. The half-life for 111 In in four control rats was 18·7 hr and in five rats treated with 5-HTP was 17·8 hr. In rabbits the half-life was 20·4 hr for eight control and 21·2 hr for seven treated with 5-HTP. In the dogs the half-life was 21·0 hr for control and 27·7 hr for experiments with 5-HTP. In control rats, the 14 C behaved like the 111 In. However, in control rabbits the half-life for 14 C was 38·0 hr which is significantly longer than for 111 In ( P < 0·005). 14 C also disappeared more slowly than the 111 In in the dogs. 3. In all species treatment with 5-HTP accelerated the disappearance of the 14 C approximately three-fold. This was not a reserpine-like effect because the platelets contained more, not less 5-HT than usual. 4. In an attempt to discover the fate of 5-HT disappearing from circulating platelets, experiments were made in which platelets from one rat were doubly labelled, and were then injected into two other rats from the identical strain; one of the recipients received daily I.P. injections of 20 mg/kg of 5-HTP. The other rat in each pair acted as a control. 5. Results from twelve control rats showed that the 14 C/ 111 In ratio in several tissues deviated from that found in platelets. Deviations occurred in both directions; in the spleen, liver and kidney the ratio was significantly lower than in the platelets ( P < 0·01), whereas in the adrenals, thyroid, bladder and gut the ratio was significantly higher ( P < 0·05 for thyroid, < 0·01 for others). In the gut, however, the ratio was significantly raised ( P < 0·01) only at 5 hr. 6. Administration of unlabelled 5-HTP to another twelve rats
doi_str_mv 10.1113/jphysiol.1983.sp014750
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E. ; Wyllie, J. H.</creator><creatorcontrib>Osim, E. E. ; Wyllie, J. H.</creatorcontrib><description>1. Platelets were obtained from three species of animal: rats, rabbits and dogs. They were labelled with 111 In oxine to tag individual platelets and with 14 C-labelled 5-hydroxytryptamine (5-HT). Doubly labelled platelets from rabbits and dogs were returned to their donors; in the case of rats the platelets were injected intravenously into other, identical rats. At time intervals from 2 to 64 hr, blood samples were drawn and platelets were collected. 111 In and 14 C were separately counted. In some experiments animals received the 5-HT precursor, 5-hydroxytryptophan (5-HTP) I.P. (for rats and rabbits) or subcutaneously (for dogs) in a dose of 20 mg/kg daily to accelerate synthesis of 5-HT. 2. 111 In disappeared in approximately an exponential fashion in all experiments and the rate of disappearance was not affected by treatment with 5-HTP. The half-life for 111 In in four control rats was 18·7 hr and in five rats treated with 5-HTP was 17·8 hr. In rabbits the half-life was 20·4 hr for eight control and 21·2 hr for seven treated with 5-HTP. In the dogs the half-life was 21·0 hr for control and 27·7 hr for experiments with 5-HTP. In control rats, the 14 C behaved like the 111 In. However, in control rabbits the half-life for 14 C was 38·0 hr which is significantly longer than for 111 In ( P &lt; 0·005). 14 C also disappeared more slowly than the 111 In in the dogs. 3. In all species treatment with 5-HTP accelerated the disappearance of the 14 C approximately three-fold. This was not a reserpine-like effect because the platelets contained more, not less 5-HT than usual. 4. In an attempt to discover the fate of 5-HT disappearing from circulating platelets, experiments were made in which platelets from one rat were doubly labelled, and were then injected into two other rats from the identical strain; one of the recipients received daily I.P. injections of 20 mg/kg of 5-HTP. The other rat in each pair acted as a control. 5. Results from twelve control rats showed that the 14 C/ 111 In ratio in several tissues deviated from that found in platelets. Deviations occurred in both directions; in the spleen, liver and kidney the ratio was significantly lower than in the platelets ( P &lt; 0·01), whereas in the adrenals, thyroid, bladder and gut the ratio was significantly higher ( P &lt; 0·05 for thyroid, &lt; 0·01 for others). In the gut, however, the ratio was significantly raised ( P &lt; 0·01) only at 5 hr. 6. Administration of unlabelled 5-HTP to another twelve rats greatly reduced the 14 C in platelets. Under these conditions many tissues in addition to those above had a higher ratio of 14 C/ 111 In than platelets. These tissues included muscle, skin, salivary gland, kidney, heart, aorta, testis and seminal vesicle. As with platelets, the absolute counts of 14 C/g of tissue decreased significantly after 5-HTP administration (platelets by 67%, brain by 56%, pancreas by 49%, lungs by 39%, liver by 37%, kidney by 29%, testis by 23% and seminal vesicle by 22%). On the other hand, there were significant rises of 93% in the skin and 21% in the muscle. Paper chromatography showed that 73-86% of the 14 C in tissues still behaved like 5-HT, except in the bladder and adrenals which contained unidentified material. 7. It is concluded that under normal conditions platelets deposit 5-HT in specific tissues, notably gut, adrenals and thyroid. When unlabelled 5-HTP is administered, the labelled 5-HT is deposited in a variety of tissues, and especially in the skin.</description><identifier>ISSN: 0022-3751</identifier><identifier>EISSN: 1469-7793</identifier><identifier>DOI: 10.1113/jphysiol.1983.sp014750</identifier><identifier>PMID: 6411907</identifier><language>eng</language><publisher>England: The Physiological Society</publisher><subject>5-Hydroxytryptophan - pharmacology ; Animals ; Blood Platelets - metabolism ; Carbon Radioisotopes ; Dogs ; Female ; Half-Life ; Indium ; Kinetics ; Male ; Organometallic Compounds ; Oxyquinoline - analogs &amp; derivatives ; Rabbits ; Rats ; Rats, Inbred Strains ; Serotonin - blood ; Serotonin - metabolism ; Time Factors ; Tissue Distribution</subject><ispartof>The Journal of physiology, 1983-07, Vol.340 (1), p.77-90</ispartof><rights>1983 The Physiological Society</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4987-6ca6fcb26d1992cbfcd42943a8c0b6b8dcee04f985051de867bf7bcb1f0b07c13</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC1199197/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC1199197/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,727,780,784,885,27924,27925,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/6411907$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Osim, E. E.</creatorcontrib><creatorcontrib>Wyllie, J. H.</creatorcontrib><title>Loss of 5-hydroxytryptamine from mammalian circulating labelled platelets</title><title>The Journal of physiology</title><addtitle>J Physiol</addtitle><description>1. Platelets were obtained from three species of animal: rats, rabbits and dogs. They were labelled with 111 In oxine to tag individual platelets and with 14 C-labelled 5-hydroxytryptamine (5-HT). Doubly labelled platelets from rabbits and dogs were returned to their donors; in the case of rats the platelets were injected intravenously into other, identical rats. At time intervals from 2 to 64 hr, blood samples were drawn and platelets were collected. 111 In and 14 C were separately counted. In some experiments animals received the 5-HT precursor, 5-hydroxytryptophan (5-HTP) I.P. (for rats and rabbits) or subcutaneously (for dogs) in a dose of 20 mg/kg daily to accelerate synthesis of 5-HT. 2. 111 In disappeared in approximately an exponential fashion in all experiments and the rate of disappearance was not affected by treatment with 5-HTP. The half-life for 111 In in four control rats was 18·7 hr and in five rats treated with 5-HTP was 17·8 hr. In rabbits the half-life was 20·4 hr for eight control and 21·2 hr for seven treated with 5-HTP. In the dogs the half-life was 21·0 hr for control and 27·7 hr for experiments with 5-HTP. In control rats, the 14 C behaved like the 111 In. However, in control rabbits the half-life for 14 C was 38·0 hr which is significantly longer than for 111 In ( P &lt; 0·005). 14 C also disappeared more slowly than the 111 In in the dogs. 3. In all species treatment with 5-HTP accelerated the disappearance of the 14 C approximately three-fold. This was not a reserpine-like effect because the platelets contained more, not less 5-HT than usual. 4. In an attempt to discover the fate of 5-HT disappearing from circulating platelets, experiments were made in which platelets from one rat were doubly labelled, and were then injected into two other rats from the identical strain; one of the recipients received daily I.P. injections of 20 mg/kg of 5-HTP. The other rat in each pair acted as a control. 5. Results from twelve control rats showed that the 14 C/ 111 In ratio in several tissues deviated from that found in platelets. Deviations occurred in both directions; in the spleen, liver and kidney the ratio was significantly lower than in the platelets ( P &lt; 0·01), whereas in the adrenals, thyroid, bladder and gut the ratio was significantly higher ( P &lt; 0·05 for thyroid, &lt; 0·01 for others). In the gut, however, the ratio was significantly raised ( P &lt; 0·01) only at 5 hr. 6. Administration of unlabelled 5-HTP to another twelve rats greatly reduced the 14 C in platelets. Under these conditions many tissues in addition to those above had a higher ratio of 14 C/ 111 In than platelets. These tissues included muscle, skin, salivary gland, kidney, heart, aorta, testis and seminal vesicle. As with platelets, the absolute counts of 14 C/g of tissue decreased significantly after 5-HTP administration (platelets by 67%, brain by 56%, pancreas by 49%, lungs by 39%, liver by 37%, kidney by 29%, testis by 23% and seminal vesicle by 22%). On the other hand, there were significant rises of 93% in the skin and 21% in the muscle. Paper chromatography showed that 73-86% of the 14 C in tissues still behaved like 5-HT, except in the bladder and adrenals which contained unidentified material. 7. It is concluded that under normal conditions platelets deposit 5-HT in specific tissues, notably gut, adrenals and thyroid. When unlabelled 5-HTP is administered, the labelled 5-HT is deposited in a variety of tissues, and especially in the skin.</description><subject>5-Hydroxytryptophan - pharmacology</subject><subject>Animals</subject><subject>Blood Platelets - metabolism</subject><subject>Carbon Radioisotopes</subject><subject>Dogs</subject><subject>Female</subject><subject>Half-Life</subject><subject>Indium</subject><subject>Kinetics</subject><subject>Male</subject><subject>Organometallic Compounds</subject><subject>Oxyquinoline - analogs &amp; derivatives</subject><subject>Rabbits</subject><subject>Rats</subject><subject>Rats, Inbred Strains</subject><subject>Serotonin - blood</subject><subject>Serotonin - metabolism</subject><subject>Time Factors</subject><subject>Tissue Distribution</subject><issn>0022-3751</issn><issn>1469-7793</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1983</creationdate><recordtype>article</recordtype><recordid>eNqNUctu1DAUtRCoDIVPAGXFLsO9edjxBqmqeBSNBIuytmzHnrhy4mBnKPl7PJppVXasLN3z8D33EPIOYYuI9Ye7eViTC36LvKu3aQZsWAvPyAYbykvGeP2cbACqqqxZiy_Jq5TuALAGzi_IBW0QObANudmFlIpgi7Yc1j6GP-sS13mRo5tMYWMYi1GOo_ROToV2UR-8XNy0L7xUxnvTF3MeGG-W9Jq8sNIn8-b8XpKfnz_dXn8td9-_3Fxf7Urd8I6VVEtqtapoj5xXWlndNxVvatlpUFR1vTYGGsu7FlrsTUeZskxphRYUMI31Jfl48p0PajSZPi1RejFHN8q4iiCd-BeZ3CD24bfIiTlylg3enw1i-HUwaRGjSzqnkZMJhyQ6oFVHW8hEeiLqmI8UjX38BEEcSxAPJYhjCeKhhCx8-3TFR9n56hm_OuH3zpv1P13F7bcfx0HdALInKQa3H-5dNOKkSkE7s6wi0wSKTPwL2WKrvw</recordid><startdate>19830701</startdate><enddate>19830701</enddate><creator>Osim, E. E.</creator><creator>Wyllie, J. H.</creator><general>The Physiological Society</general><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><scope>5PM</scope></search><sort><creationdate>19830701</creationdate><title>Loss of 5-hydroxytryptamine from mammalian circulating labelled platelets</title><author>Osim, E. E. ; Wyllie, J. H.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4987-6ca6fcb26d1992cbfcd42943a8c0b6b8dcee04f985051de867bf7bcb1f0b07c13</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1983</creationdate><topic>5-Hydroxytryptophan - pharmacology</topic><topic>Animals</topic><topic>Blood Platelets - metabolism</topic><topic>Carbon Radioisotopes</topic><topic>Dogs</topic><topic>Female</topic><topic>Half-Life</topic><topic>Indium</topic><topic>Kinetics</topic><topic>Male</topic><topic>Organometallic Compounds</topic><topic>Oxyquinoline - analogs &amp; derivatives</topic><topic>Rabbits</topic><topic>Rats</topic><topic>Rats, Inbred Strains</topic><topic>Serotonin - blood</topic><topic>Serotonin - metabolism</topic><topic>Time Factors</topic><topic>Tissue Distribution</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Osim, E. E.</creatorcontrib><creatorcontrib>Wyllie, J. H.</creatorcontrib><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><collection>PubMed Central (Full Participant titles)</collection><jtitle>The Journal of physiology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Osim, E. E.</au><au>Wyllie, J. H.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Loss of 5-hydroxytryptamine from mammalian circulating labelled platelets</atitle><jtitle>The Journal of physiology</jtitle><addtitle>J Physiol</addtitle><date>1983-07-01</date><risdate>1983</risdate><volume>340</volume><issue>1</issue><spage>77</spage><epage>90</epage><pages>77-90</pages><issn>0022-3751</issn><eissn>1469-7793</eissn><abstract>1. Platelets were obtained from three species of animal: rats, rabbits and dogs. They were labelled with 111 In oxine to tag individual platelets and with 14 C-labelled 5-hydroxytryptamine (5-HT). Doubly labelled platelets from rabbits and dogs were returned to their donors; in the case of rats the platelets were injected intravenously into other, identical rats. At time intervals from 2 to 64 hr, blood samples were drawn and platelets were collected. 111 In and 14 C were separately counted. In some experiments animals received the 5-HT precursor, 5-hydroxytryptophan (5-HTP) I.P. (for rats and rabbits) or subcutaneously (for dogs) in a dose of 20 mg/kg daily to accelerate synthesis of 5-HT. 2. 111 In disappeared in approximately an exponential fashion in all experiments and the rate of disappearance was not affected by treatment with 5-HTP. The half-life for 111 In in four control rats was 18·7 hr and in five rats treated with 5-HTP was 17·8 hr. In rabbits the half-life was 20·4 hr for eight control and 21·2 hr for seven treated with 5-HTP. In the dogs the half-life was 21·0 hr for control and 27·7 hr for experiments with 5-HTP. In control rats, the 14 C behaved like the 111 In. However, in control rabbits the half-life for 14 C was 38·0 hr which is significantly longer than for 111 In ( P &lt; 0·005). 14 C also disappeared more slowly than the 111 In in the dogs. 3. In all species treatment with 5-HTP accelerated the disappearance of the 14 C approximately three-fold. This was not a reserpine-like effect because the platelets contained more, not less 5-HT than usual. 4. In an attempt to discover the fate of 5-HT disappearing from circulating platelets, experiments were made in which platelets from one rat were doubly labelled, and were then injected into two other rats from the identical strain; one of the recipients received daily I.P. injections of 20 mg/kg of 5-HTP. The other rat in each pair acted as a control. 5. Results from twelve control rats showed that the 14 C/ 111 In ratio in several tissues deviated from that found in platelets. Deviations occurred in both directions; in the spleen, liver and kidney the ratio was significantly lower than in the platelets ( P &lt; 0·01), whereas in the adrenals, thyroid, bladder and gut the ratio was significantly higher ( P &lt; 0·05 for thyroid, &lt; 0·01 for others). In the gut, however, the ratio was significantly raised ( P &lt; 0·01) only at 5 hr. 6. Administration of unlabelled 5-HTP to another twelve rats greatly reduced the 14 C in platelets. Under these conditions many tissues in addition to those above had a higher ratio of 14 C/ 111 In than platelets. These tissues included muscle, skin, salivary gland, kidney, heart, aorta, testis and seminal vesicle. As with platelets, the absolute counts of 14 C/g of tissue decreased significantly after 5-HTP administration (platelets by 67%, brain by 56%, pancreas by 49%, lungs by 39%, liver by 37%, kidney by 29%, testis by 23% and seminal vesicle by 22%). On the other hand, there were significant rises of 93% in the skin and 21% in the muscle. Paper chromatography showed that 73-86% of the 14 C in tissues still behaved like 5-HT, except in the bladder and adrenals which contained unidentified material. 7. It is concluded that under normal conditions platelets deposit 5-HT in specific tissues, notably gut, adrenals and thyroid. When unlabelled 5-HTP is administered, the labelled 5-HT is deposited in a variety of tissues, and especially in the skin.</abstract><cop>England</cop><pub>The Physiological Society</pub><pmid>6411907</pmid><doi>10.1113/jphysiol.1983.sp014750</doi><tpages>14</tpages><oa>free_for_read</oa></addata></record>
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subjects 5-Hydroxytryptophan - pharmacology
Animals
Blood Platelets - metabolism
Carbon Radioisotopes
Dogs
Female
Half-Life
Indium
Kinetics
Male
Organometallic Compounds
Oxyquinoline - analogs & derivatives
Rabbits
Rats
Rats, Inbred Strains
Serotonin - blood
Serotonin - metabolism
Time Factors
Tissue Distribution
title Loss of 5-hydroxytryptamine from mammalian circulating labelled platelets
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