Effects of nonapeptide antagonists on oxytocin- and arginine-vasopressin-induced analgesia in mice

J. D. Caldwell; G. A. Mason; D. A. Stanley; G. Jerdack; V. J. Hruby; P. Hill; A. J. Prange; C. A. Pedersen

doi:10.1016/0167-0115(87)90011-5

Effects of nonapeptide antagonists on oxytocin- and arginine-vasopressin-induced analgesia in mice

J. D. Caldwell, G. A. Mason, D. A. Stanley, G. Jerdack, V. J. Hruby, P. Hill, A. J. Prange, C. A. Pedersen

Chemistry and Biochemistry

Research output: Contribution to journal › Article › peer-review

36 Scopus citations

Abstract

Several peptides, including arginine-vasopressin (AVP), neurotensin, and substance P, produce analgesia that is not mediated by opiate systems. Using the hot plate test, we studied the analgesic effects of intracisternal (i.c.) administration of various doses of the nonapeptide oxytocin (OXY) in Swiss-Webster mice. We found that OXY (1-4 μg) significantly increased the latency of animals to jump or lick their paws after placement on a hot plate. This effect was not blocked by naloxone pretreatment, which suggests that it is not opiate dependent. Using the hot plate test, we confirmed that AVP (1 and 4 μg) also produces analgesia. We then studied the analgesia produced by OXY and by AVP using 3 nonapeptide analogues with antagonist properties: [Pen¹, LpMePhe², Thr⁴, Orn⁸]OXY (PLMPTO-OXY) that has anti-oxytocic properties in the uterine contraction assay, d(CH₂)₅Tyr(Me)AVP (dTM-AVP) which antagonizes the antidiuretic properties of AVP and d(CH₂)₅d-Ile²,Abu⁴-AVP (dIA-AVP) which antagonizes the vasopressor effects of AVP. Simultaneous administration of PLMPTO-OXY completely blocked the analgesia produced by OXY whereas the antidiuretic antagonist dIA-AVP partially blocked OXY-induced analgesia and dTM-AVP had no effect. None of the antagonists used blocked AVP-induced analgesia. We concluded that the neural systems mediating the analgesic effects of i.c. OXY differ from those for AVP.

Original language	English (US)
Pages (from-to)	233-241
Number of pages	9
Journal	Regulatory Peptides
Volume	18
Issue number	3-4
DOIs	https://doi.org/10.1016/0167-0115(87)90011-5
State	Published - Aug 17 1987

Keywords

Analgesia
Antagonist
Intracisternal
Mouse
Oxytocin
Vasopressin

ASJC Scopus subject areas

Biochemistry
Physiology
Endocrinology
Clinical Biochemistry
Cellular and Molecular Neuroscience

Access to Document

10.1016/0167-0115(87)90011-5

Cite this

@article{54cae140aea84cfd909bed2bd4916176,

title = "Effects of nonapeptide antagonists on oxytocin- and arginine-vasopressin-induced analgesia in mice",

abstract = "Several peptides, including arginine-vasopressin (AVP), neurotensin, and substance P, produce analgesia that is not mediated by opiate systems. Using the hot plate test, we studied the analgesic effects of intracisternal (i.c.) administration of various doses of the nonapeptide oxytocin (OXY) in Swiss-Webster mice. We found that OXY (1-4 μg) significantly increased the latency of animals to jump or lick their paws after placement on a hot plate. This effect was not blocked by naloxone pretreatment, which suggests that it is not opiate dependent. Using the hot plate test, we confirmed that AVP (1 and 4 μg) also produces analgesia. We then studied the analgesia produced by OXY and by AVP using 3 nonapeptide analogues with antagonist properties: [Pen1, LpMePhe2, Thr4, Orn8]OXY (PLMPTO-OXY) that has anti-oxytocic properties in the uterine contraction assay, d(CH2)5Tyr(Me)AVP (dTM-AVP) which antagonizes the antidiuretic properties of AVP and d(CH2)5d-Ile2,Abu4-AVP (dIA-AVP) which antagonizes the vasopressor effects of AVP. Simultaneous administration of PLMPTO-OXY completely blocked the analgesia produced by OXY whereas the antidiuretic antagonist dIA-AVP partially blocked OXY-induced analgesia and dTM-AVP had no effect. None of the antagonists used blocked AVP-induced analgesia. We concluded that the neural systems mediating the analgesic effects of i.c. OXY differ from those for AVP.",

keywords = "Analgesia, Antagonist, Intracisternal, Mouse, Oxytocin, Vasopressin",

author = "Caldwell, {J. D.} and Mason, {G. A.} and Stanley, {D. A.} and G. Jerdack and Hruby, {V. J.} and P. Hill and Prange, {A. J.} and Pedersen, {C. A.}",

note = "Funding Information: This research was supported by NIMH grants MH 33127. HD-16159 and MH 1427. We would like to thank Dr. Maurice Manning of the Department of Biochemistry, Medical College of Ohio, Toledo for providing the vasopressin antagonist analogues used in this study. We are grateful to Mr. Ossie Hatley and Ms. Elizabeth Little for technical assistance and to Ms. Debbie Lowery and Ms. Rosaleen Salvo for their help in the preparation of this manuscript.",

year = "1987",

month = aug,

day = "17",

doi = "10.1016/0167-0115(87)90011-5",

language = "English (US)",

volume = "18",

pages = "233--241",

journal = "Regulatory Peptides",

issn = "0167-0115",

publisher = "Elsevier",

number = "3-4",

}

TY - JOUR

T1 - Effects of nonapeptide antagonists on oxytocin- and arginine-vasopressin-induced analgesia in mice

AU - Caldwell, J. D.

AU - Mason, G. A.

AU - Stanley, D. A.

AU - Jerdack, G.

AU - Hruby, V. J.

AU - Hill, P.

AU - Prange, A. J.

AU - Pedersen, C. A.

N1 - Funding Information: This research was supported by NIMH grants MH 33127. HD-16159 and MH 1427. We would like to thank Dr. Maurice Manning of the Department of Biochemistry, Medical College of Ohio, Toledo for providing the vasopressin antagonist analogues used in this study. We are grateful to Mr. Ossie Hatley and Ms. Elizabeth Little for technical assistance and to Ms. Debbie Lowery and Ms. Rosaleen Salvo for their help in the preparation of this manuscript.

PY - 1987/8/17

Y1 - 1987/8/17

N2 - Several peptides, including arginine-vasopressin (AVP), neurotensin, and substance P, produce analgesia that is not mediated by opiate systems. Using the hot plate test, we studied the analgesic effects of intracisternal (i.c.) administration of various doses of the nonapeptide oxytocin (OXY) in Swiss-Webster mice. We found that OXY (1-4 μg) significantly increased the latency of animals to jump or lick their paws after placement on a hot plate. This effect was not blocked by naloxone pretreatment, which suggests that it is not opiate dependent. Using the hot plate test, we confirmed that AVP (1 and 4 μg) also produces analgesia. We then studied the analgesia produced by OXY and by AVP using 3 nonapeptide analogues with antagonist properties: [Pen1, LpMePhe2, Thr4, Orn8]OXY (PLMPTO-OXY) that has anti-oxytocic properties in the uterine contraction assay, d(CH2)5Tyr(Me)AVP (dTM-AVP) which antagonizes the antidiuretic properties of AVP and d(CH2)5d-Ile2,Abu4-AVP (dIA-AVP) which antagonizes the vasopressor effects of AVP. Simultaneous administration of PLMPTO-OXY completely blocked the analgesia produced by OXY whereas the antidiuretic antagonist dIA-AVP partially blocked OXY-induced analgesia and dTM-AVP had no effect. None of the antagonists used blocked AVP-induced analgesia. We concluded that the neural systems mediating the analgesic effects of i.c. OXY differ from those for AVP.

AB - Several peptides, including arginine-vasopressin (AVP), neurotensin, and substance P, produce analgesia that is not mediated by opiate systems. Using the hot plate test, we studied the analgesic effects of intracisternal (i.c.) administration of various doses of the nonapeptide oxytocin (OXY) in Swiss-Webster mice. We found that OXY (1-4 μg) significantly increased the latency of animals to jump or lick their paws after placement on a hot plate. This effect was not blocked by naloxone pretreatment, which suggests that it is not opiate dependent. Using the hot plate test, we confirmed that AVP (1 and 4 μg) also produces analgesia. We then studied the analgesia produced by OXY and by AVP using 3 nonapeptide analogues with antagonist properties: [Pen1, LpMePhe2, Thr4, Orn8]OXY (PLMPTO-OXY) that has anti-oxytocic properties in the uterine contraction assay, d(CH2)5Tyr(Me)AVP (dTM-AVP) which antagonizes the antidiuretic properties of AVP and d(CH2)5d-Ile2,Abu4-AVP (dIA-AVP) which antagonizes the vasopressor effects of AVP. Simultaneous administration of PLMPTO-OXY completely blocked the analgesia produced by OXY whereas the antidiuretic antagonist dIA-AVP partially blocked OXY-induced analgesia and dTM-AVP had no effect. None of the antagonists used blocked AVP-induced analgesia. We concluded that the neural systems mediating the analgesic effects of i.c. OXY differ from those for AVP.

KW - Analgesia

KW - Antagonist

KW - Intracisternal

KW - Mouse

KW - Oxytocin

KW - Vasopressin

UR - http://www.scopus.com/inward/record.url?scp=0023230895&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0023230895&partnerID=8YFLogxK

U2 - 10.1016/0167-0115(87)90011-5

DO - 10.1016/0167-0115(87)90011-5

M3 - Article

C2 - 3671785

AN - SCOPUS:0023230895

VL - 18

SP - 233

EP - 241

JO - Regulatory Peptides

JF - Regulatory Peptides

SN - 0167-0115

IS - 3-4

ER -

Effects of nonapeptide antagonists on oxytocin- and arginine-vasopressin-induced analgesia in mice

Abstract

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this