Neurotensin Excites Periaqueductal Gray Neurons Projecting to the Rostral Ventromedial Medulla
1 Department of Anesthesiology and 3 Department of Neurology, Chang Gung Memorial Hospital; and 2 Department of Anatomy and 4 Department of Physiology, Chang Gung University School of Medicine, Kwei-San, Tao-Yuan, Taiwan, R.O.C. Li, Allen H., Hwa-Min Hwang, Peter P. Tan, Tony Wu, and Hung-Li...
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| Veröffentlicht in: | Journal of neurophysiology 2001-04, Vol.85 (4), p.1479-1488 |
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| creator | Li, Allen H Hwang, Hwa-Min Tan, Peter P Wu, Tony Wang, Hung-Li |
| description | 1 Department of Anesthesiology and
3 Department of Neurology, Chang Gung Memorial
Hospital; and 2 Department of Anatomy and
4 Department of Physiology, Chang
Gung University School of Medicine, Kwei-San, Tao-Yuan, Taiwan, R.O.C.
Li, Allen H.,
Hwa-Min Hwang,
Peter P. Tan,
Tony Wu, and
Hung-Li Wang.
Neurotensin Excites Periaqueductal Gray Neurons Projecting to
the Rostral Ventromedial Medulla. J. Neurophysiol. 85: 1479-1488, 2001. Microinjection of neurotensin
into the midbrain periaqueductal gray (PAG) produces a potent and
naloxone-insensitive analgesic effect. To test the hypothesis that
neurotensin induces the analgesic effect by activating the PAG-rostral
ventromedial medulla (RVM) descending antinociceptive pathway, PAG
neurons that project to RVM (PAG-RVM) were identified by microinjecting
DiI C18 , a retrograde tracing dye, into the rat
RVM. Subsequently, fluorescently labeled PAG-RVM projection neurons
were acutely dissociated and selected for whole cell patch-clamp
recordings. During current-clamp recordings, neurotensin depolarized
retrogradely labeled PAG-RVM neurons and evoked action potentials.
Voltage-clamp recordings indicated that neurotensin excited PAG-RVM
neurons by opening the voltage-insensitive and nonselective cation
channels. Both SR 48692, a selective NTR-1 antagonist, and SR 142948A,
a nonselective antagonist of NTR-1 and NTR-2, failed to prevent
neurotensin from exciting PAG-RVM neurons. Neurotensin failed to evoke
cationic currents after internally perfusing PAG-RVM projection neurons
with GDP- -S or
anti-G q/11 antiserum.
Cellular Ca 2+ fluorescence measurement using
fura-2 indicated that neurotensin rapidly induced
Ca 2+ release from intracellular stores of PAG-RVM
neurons. Neurotensin-evoked cationic currents were blocked by heparin,
an IP 3 receptor antagonist, and
1,2-bis(2-aminophenoxy)ethane- N,N,N',N' -tetraacetic acid
(BAPTA), a fast chelator of Ca 2+ . These results
suggest that by activating a novel subtype of neurotensin receptors,
neurotensin depolarizes and excites PAG-RVM projection neurons through
enhancing Ca 2+ -dependent nonselective cationic
conductance. The coupling mechanism via
G q/11 proteins is likely
to involve the production of IP 3 , and subsequent
IP 3 -evoked Ca 2+ release
leads to the opening of nonselective cation channels. |
| doi_str_mv | 10.1152/jn.2001.85.4.1479 |
| format | Article |
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3 Department of Neurology, Chang Gung Memorial
Hospital; and 2 Department of Anatomy and
4 Department of Physiology, Chang
Gung University School of Medicine, Kwei-San, Tao-Yuan, Taiwan, R.O.C.
Li, Allen H.,
Hwa-Min Hwang,
Peter P. Tan,
Tony Wu, and
Hung-Li Wang.
Neurotensin Excites Periaqueductal Gray Neurons Projecting to
the Rostral Ventromedial Medulla. J. Neurophysiol. 85: 1479-1488, 2001. Microinjection of neurotensin
into the midbrain periaqueductal gray (PAG) produces a potent and
naloxone-insensitive analgesic effect. To test the hypothesis that
neurotensin induces the analgesic effect by activating the PAG-rostral
ventromedial medulla (RVM) descending antinociceptive pathway, PAG
neurons that project to RVM (PAG-RVM) were identified by microinjecting
DiI C18 , a retrograde tracing dye, into the rat
RVM. Subsequently, fluorescently labeled PAG-RVM projection neurons
were acutely dissociated and selected for whole cell patch-clamp
recordings. During current-clamp recordings, neurotensin depolarized
retrogradely labeled PAG-RVM neurons and evoked action potentials.
Voltage-clamp recordings indicated that neurotensin excited PAG-RVM
neurons by opening the voltage-insensitive and nonselective cation
channels. Both SR 48692, a selective NTR-1 antagonist, and SR 142948A,
a nonselective antagonist of NTR-1 and NTR-2, failed to prevent
neurotensin from exciting PAG-RVM neurons. Neurotensin failed to evoke
cationic currents after internally perfusing PAG-RVM projection neurons
with GDP- -S or
anti-G q/11 antiserum.
Cellular Ca 2+ fluorescence measurement using
fura-2 indicated that neurotensin rapidly induced
Ca 2+ release from intracellular stores of PAG-RVM
neurons. Neurotensin-evoked cationic currents were blocked by heparin,
an IP 3 receptor antagonist, and
1,2-bis(2-aminophenoxy)ethane- N,N,N',N' -tetraacetic acid
(BAPTA), a fast chelator of Ca 2+ . These results
suggest that by activating a novel subtype of neurotensin receptors,
neurotensin depolarizes and excites PAG-RVM projection neurons through
enhancing Ca 2+ -dependent nonselective cationic
conductance. The coupling mechanism via
G q/11 proteins is likely
to involve the production of IP 3 , and subsequent
IP 3 -evoked Ca 2+ release
leads to the opening of nonselective cation channels.</description><identifier>ISSN: 0022-3077</identifier><identifier>EISSN: 1522-1598</identifier><identifier>DOI: 10.1152/jn.2001.85.4.1479</identifier><identifier>PMID: 11287471</identifier><language>eng</language><publisher>United States: Am Phys Soc</publisher><subject>Animals ; Calcium - metabolism ; Cations - metabolism ; Electric Conductivity ; GTP-Binding Proteins - physiology ; Inositol 1,4,5-Trisphosphate - pharmacology ; Ion Channels - physiology ; Medulla Oblongata - physiology ; Neurons - drug effects ; Neurons - physiology ; Neurotensin - pharmacology ; Periaqueductal Gray - cytology ; Periaqueductal Gray - drug effects ; Periaqueductal Gray - physiology ; Rats ; Receptors, Neurotensin - physiology ; Synaptic Transmission - physiology</subject><ispartof>Journal of neurophysiology, 2001-04, Vol.85 (4), p.1479-1488</ispartof><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c404t-2b5fa7036150a7e9a3fab89eb3d7507aa01ebedf6e492d8b3e51ec15acd2ed5c3</citedby><cites>FETCH-LOGICAL-c404t-2b5fa7036150a7e9a3fab89eb3d7507aa01ebedf6e492d8b3e51ec15acd2ed5c3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,3039,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/11287471$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Li, Allen H</creatorcontrib><creatorcontrib>Hwang, Hwa-Min</creatorcontrib><creatorcontrib>Tan, Peter P</creatorcontrib><creatorcontrib>Wu, Tony</creatorcontrib><creatorcontrib>Wang, Hung-Li</creatorcontrib><title>Neurotensin Excites Periaqueductal Gray Neurons Projecting to the Rostral Ventromedial Medulla</title><title>Journal of neurophysiology</title><addtitle>J Neurophysiol</addtitle><description> 1 Department of Anesthesiology and
3 Department of Neurology, Chang Gung Memorial
Hospital; and 2 Department of Anatomy and
4 Department of Physiology, Chang
Gung University School of Medicine, Kwei-San, Tao-Yuan, Taiwan, R.O.C.
Li, Allen H.,
Hwa-Min Hwang,
Peter P. Tan,
Tony Wu, and
Hung-Li Wang.
Neurotensin Excites Periaqueductal Gray Neurons Projecting to
the Rostral Ventromedial Medulla. J. Neurophysiol. 85: 1479-1488, 2001. Microinjection of neurotensin
into the midbrain periaqueductal gray (PAG) produces a potent and
naloxone-insensitive analgesic effect. To test the hypothesis that
neurotensin induces the analgesic effect by activating the PAG-rostral
ventromedial medulla (RVM) descending antinociceptive pathway, PAG
neurons that project to RVM (PAG-RVM) were identified by microinjecting
DiI C18 , a retrograde tracing dye, into the rat
RVM. Subsequently, fluorescently labeled PAG-RVM projection neurons
were acutely dissociated and selected for whole cell patch-clamp
recordings. During current-clamp recordings, neurotensin depolarized
retrogradely labeled PAG-RVM neurons and evoked action potentials.
Voltage-clamp recordings indicated that neurotensin excited PAG-RVM
neurons by opening the voltage-insensitive and nonselective cation
channels. Both SR 48692, a selective NTR-1 antagonist, and SR 142948A,
a nonselective antagonist of NTR-1 and NTR-2, failed to prevent
neurotensin from exciting PAG-RVM neurons. Neurotensin failed to evoke
cationic currents after internally perfusing PAG-RVM projection neurons
with GDP- -S or
anti-G q/11 antiserum.
Cellular Ca 2+ fluorescence measurement using
fura-2 indicated that neurotensin rapidly induced
Ca 2+ release from intracellular stores of PAG-RVM
neurons. Neurotensin-evoked cationic currents were blocked by heparin,
an IP 3 receptor antagonist, and
1,2-bis(2-aminophenoxy)ethane- N,N,N',N' -tetraacetic acid
(BAPTA), a fast chelator of Ca 2+ . These results
suggest that by activating a novel subtype of neurotensin receptors,
neurotensin depolarizes and excites PAG-RVM projection neurons through
enhancing Ca 2+ -dependent nonselective cationic
conductance. The coupling mechanism via
G q/11 proteins is likely
to involve the production of IP 3 , and subsequent
IP 3 -evoked Ca 2+ release
leads to the opening of nonselective cation channels.</description><subject>Animals</subject><subject>Calcium - metabolism</subject><subject>Cations - metabolism</subject><subject>Electric Conductivity</subject><subject>GTP-Binding Proteins - physiology</subject><subject>Inositol 1,4,5-Trisphosphate - pharmacology</subject><subject>Ion Channels - physiology</subject><subject>Medulla Oblongata - physiology</subject><subject>Neurons - drug effects</subject><subject>Neurons - physiology</subject><subject>Neurotensin - pharmacology</subject><subject>Periaqueductal Gray - cytology</subject><subject>Periaqueductal Gray - drug effects</subject><subject>Periaqueductal Gray - physiology</subject><subject>Rats</subject><subject>Receptors, Neurotensin - physiology</subject><subject>Synaptic Transmission - physiology</subject><issn>0022-3077</issn><issn>1522-1598</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2001</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkE1v1DAURS0EokPhB7BBWcFqgl9s184SVW1BKh9ChSWW47zMeJSJB9sRnX_PG2ZEV4iVY-fcq6vD2EvgNYBq3m6muuEcaqNqWYPU7SO2oPdmCao1j9mCc_oWXOsz9iznDedcK948ZWcAjdFSw4L9-IRzigWnHKbq6t6Hgrn6gim4nzP2sy9urG6S21d_uIn-pbhBX8K0qkqsyhqrrzGXRNh3nEqKW-wDXT5SeBzdc_ZkcGPGF6fznH27vrq7fL-8_Xzz4fLd7dJLLsuy6dTgNBcXoLjT2DoxuM602ImeFmvnOGCH_XCBsm160wlUgB6U832DvfLinL0-9u5SpOG52G3IHmnBhHHOVlM5SJD_BcFww4URBMIR9CnmnHCwuxS2Lu0tcHuwbzeTPdi3RllpD_Yp8-pUPnfk4SFx0k2AOALrsFr_Cgntbr3PIY5xtbfXJOwO7wsV_620u36g1Jt_p2jFw4DfoDOjFg</recordid><startdate>20010401</startdate><enddate>20010401</enddate><creator>Li, Allen H</creator><creator>Hwang, Hwa-Min</creator><creator>Tan, Peter P</creator><creator>Wu, Tony</creator><creator>Wang, Hung-Li</creator><general>Am Phys Soc</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>7TK</scope><scope>7X8</scope></search><sort><creationdate>20010401</creationdate><title>Neurotensin Excites Periaqueductal Gray Neurons Projecting to the Rostral Ventromedial Medulla</title><author>Li, Allen H ; Hwang, Hwa-Min ; Tan, Peter P ; Wu, Tony ; Wang, Hung-Li</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c404t-2b5fa7036150a7e9a3fab89eb3d7507aa01ebedf6e492d8b3e51ec15acd2ed5c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2001</creationdate><topic>Animals</topic><topic>Calcium - metabolism</topic><topic>Cations - metabolism</topic><topic>Electric Conductivity</topic><topic>GTP-Binding Proteins - physiology</topic><topic>Inositol 1,4,5-Trisphosphate - pharmacology</topic><topic>Ion Channels - physiology</topic><topic>Medulla Oblongata - physiology</topic><topic>Neurons - drug effects</topic><topic>Neurons - physiology</topic><topic>Neurotensin - pharmacology</topic><topic>Periaqueductal Gray - cytology</topic><topic>Periaqueductal Gray - drug effects</topic><topic>Periaqueductal Gray - physiology</topic><topic>Rats</topic><topic>Receptors, Neurotensin - physiology</topic><topic>Synaptic Transmission - physiology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Li, Allen H</creatorcontrib><creatorcontrib>Hwang, Hwa-Min</creatorcontrib><creatorcontrib>Tan, Peter P</creatorcontrib><creatorcontrib>Wu, Tony</creatorcontrib><creatorcontrib>Wang, Hung-Li</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Neurosciences Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of neurophysiology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Li, Allen H</au><au>Hwang, Hwa-Min</au><au>Tan, Peter P</au><au>Wu, Tony</au><au>Wang, Hung-Li</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Neurotensin Excites Periaqueductal Gray Neurons Projecting to the Rostral Ventromedial Medulla</atitle><jtitle>Journal of neurophysiology</jtitle><addtitle>J Neurophysiol</addtitle><date>2001-04-01</date><risdate>2001</risdate><volume>85</volume><issue>4</issue><spage>1479</spage><epage>1488</epage><pages>1479-1488</pages><issn>0022-3077</issn><eissn>1522-1598</eissn><abstract> 1 Department of Anesthesiology and
3 Department of Neurology, Chang Gung Memorial
Hospital; and 2 Department of Anatomy and
4 Department of Physiology, Chang
Gung University School of Medicine, Kwei-San, Tao-Yuan, Taiwan, R.O.C.
Li, Allen H.,
Hwa-Min Hwang,
Peter P. Tan,
Tony Wu, and
Hung-Li Wang.
Neurotensin Excites Periaqueductal Gray Neurons Projecting to
the Rostral Ventromedial Medulla. J. Neurophysiol. 85: 1479-1488, 2001. Microinjection of neurotensin
into the midbrain periaqueductal gray (PAG) produces a potent and
naloxone-insensitive analgesic effect. To test the hypothesis that
neurotensin induces the analgesic effect by activating the PAG-rostral
ventromedial medulla (RVM) descending antinociceptive pathway, PAG
neurons that project to RVM (PAG-RVM) were identified by microinjecting
DiI C18 , a retrograde tracing dye, into the rat
RVM. Subsequently, fluorescently labeled PAG-RVM projection neurons
were acutely dissociated and selected for whole cell patch-clamp
recordings. During current-clamp recordings, neurotensin depolarized
retrogradely labeled PAG-RVM neurons and evoked action potentials.
Voltage-clamp recordings indicated that neurotensin excited PAG-RVM
neurons by opening the voltage-insensitive and nonselective cation
channels. Both SR 48692, a selective NTR-1 antagonist, and SR 142948A,
a nonselective antagonist of NTR-1 and NTR-2, failed to prevent
neurotensin from exciting PAG-RVM neurons. Neurotensin failed to evoke
cationic currents after internally perfusing PAG-RVM projection neurons
with GDP- -S or
anti-G q/11 antiserum.
Cellular Ca 2+ fluorescence measurement using
fura-2 indicated that neurotensin rapidly induced
Ca 2+ release from intracellular stores of PAG-RVM
neurons. Neurotensin-evoked cationic currents were blocked by heparin,
an IP 3 receptor antagonist, and
1,2-bis(2-aminophenoxy)ethane- N,N,N',N' -tetraacetic acid
(BAPTA), a fast chelator of Ca 2+ . These results
suggest that by activating a novel subtype of neurotensin receptors,
neurotensin depolarizes and excites PAG-RVM projection neurons through
enhancing Ca 2+ -dependent nonselective cationic
conductance. The coupling mechanism via
G q/11 proteins is likely
to involve the production of IP 3 , and subsequent
IP 3 -evoked Ca 2+ release
leads to the opening of nonselective cation channels.</abstract><cop>United States</cop><pub>Am Phys Soc</pub><pmid>11287471</pmid><doi>10.1152/jn.2001.85.4.1479</doi><tpages>10</tpages></addata></record> |
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| ispartof | Journal of neurophysiology, 2001-04, Vol.85 (4), p.1479-1488 |
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| language | eng |
| recordid | cdi_pubmed_primary_11287471 |
| source | MEDLINE; American Physiological Society Paid; EZB-FREE-00999 freely available EZB journals |
| subjects | Animals Calcium - metabolism Cations - metabolism Electric Conductivity GTP-Binding Proteins - physiology Inositol 1,4,5-Trisphosphate - pharmacology Ion Channels - physiology Medulla Oblongata - physiology Neurons - drug effects Neurons - physiology Neurotensin - pharmacology Periaqueductal Gray - cytology Periaqueductal Gray - drug effects Periaqueductal Gray - physiology Rats Receptors, Neurotensin - physiology Synaptic Transmission - physiology |
| title | Neurotensin Excites Periaqueductal Gray Neurons Projecting to the Rostral Ventromedial Medulla |
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