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Effects of dynorphins on body temperature of rats
Pharmacoiogical Research Commun/cations, Voi. 20, No. 7, 1988
603
EFFECTS OF DYNORPHINS ON BODYTEMPERATURE OF RATS E. Cavicchini, S. Candeletti and S. Ferri Institute of Pharmacology. University of Bologna, Irnerio 48, 40126 Bologna ~.~j words
no~ins
-
Bodytemperature
-
Opioid antagonists
-
Verapamil
After the isolation and identification of Dynorphin A (Dyn A) (Goldstein et al.
1979), other
related
to
sequences endowed with opioid
Dyn A,
activity,
have been found to derive from the
structurally-
same precursor,
prodynorphin. The purpose of the present study was to characterize the effects of Dyn A and other prodynorphin-related peptides, namely Dyn B and Dyn A-(1-32), on thermoregulation.
In addition, the involvement of Ca++ in their action was
investigated. Drugs were intracerebroventricularly ( i . c . v . ) administered in unrestrained ninsula,
male rats kept at room temperature (22~C).
San Carlos, CA) and other chemicals injected in a volume of 5 ~ I .
Rectal temperature values were taken 20 min before the tions
Peptides (Pe-
and, after, at
the intervals indicated in
i.c.v,
Figure I.
administraResults were
expressed as mean ~ SEM. Comparisons were made by Student's t - t e s t . (5
Dyn A
and 10 nmol) induced a decrease in body temperature that was maximal
min after within
administration
ana then gradually returned to
120 m i n ; Dyn A-(1-32) (2.5 and 5 nmol) caused a
controi
nmol),
values
longer a c t i v i t y
whereas Dyn B (up to 20 nmol) did not induce any significant The hypothermic effect was prevented by i . c . v ,
30
hypothermia.
administered MR 1452 (30
a preferential antagonist of the ( opioid
receptor.
Naloxone, a
preferential ~ receptor antagonist and naltrexone, its long lasting'analog, up to doses of 100 nmol,as well as MR 1453, (+)-enantiomer of antagonist MR 1452 and devoid of opioid receptors binding properties, the hypothermic effect. mia
did not antagonize
A significant reduction of Dyn A-induced hypother-
(5 pmo]) was elicited by the calcium channel blocker verapamil i.c.v.
administered (10ug). Results of the present investigation showed that i.c.v,
administered Dyn A
and Dyn A-(1-32) induce a clear-cut hypothermia in rats.
0031-6989/881070603-2/$03.00/0
The lack
of
a
© 1988 The Italian Pharmacological Society
Pharmacological Research Communications, Vol. 20, No. 7, 1988
604
1
;
~......L.-L
I
'"
!
.
; ;s so 45 e'o
P
'
io
A
1~0 TIME
Fig. 1. (C) Dyn (A) ( e ) (B) ( e ) (C) ( e ) ~p <
.~
~
'
'"'
; ¢5 ~0 4'5 ~0 AFTER
t.¢.V.
.L.
B
}
.0
INJECTION
1~0
,
,
|
C
f
I
0 15 30 4~ 60
I
so
I
1~0
(mtn)
Effect of the i.c.v, administration of (A) Dyn A, (B) Dyn A-(I-32), B on rectal temperature, in the rat. saline; ( 0 ) Dyn A 2.5 nmol; (BII) Dyn A 5 nmol;(A) Dyn A 10 nmol. saline ; ( 0 ) Dyn A-(1-32) 2.5 nmol; (M) Dyn A-(1-32) 5 nmol; sa|ine; (Z~) Dyn B 10 nmol; (I"I) Dyn B 20 nmoI. 0.05 vs control values.
significant
blockade by naloxone and naltrexone and the finding
that
MR
1452 significantly antagonized the dynorphin-induced hypothermia, indicated a ~ receptor involvement in phenomena elicited by dynorphins. The different efficacy of Dyn A, to
the
Dyn A-(1-32) and Dyn B could be ascribed
different a f f i n i t y of these fragments for the ~ opioid
receptor,
already reported by James et al. (1984), "in vitro". The longer activity of Dyn A-(I-32)
could also
comparison to reduction involvement
of
be related to
a less
Dyn A (Spampinato and Candeletti,
rapid
degradation
1985). Fina]ly
Dyn A-induced hypothermia by verapamil suggested
of Ca++in the peptide effect and supported the
existence
in the an of
relationships between Ca++movements and opioids (Ross et al., 1979). REFERENCES GOLDSTEIN. A., TACHIBANA, S., LOWNEY, L . I . , HUNKAPILLER,M., HOOD, L. (1979), Proc. Natl. Acad. Sci. USA, 76: 6666-66?0. JAMES, I.F., FISCHLI,W. and GOLDSTEIN, A. (1984), J. Pharmacol. Exp. Ther., 228~ 88-93. ROSS, D.H. and CANDENAS, H.L. (1979),Adv. Biochem. Psychopharmacol., 20: 301-336. SPAMPINATO,S. and CANDELETTI, $. (1985),European J. Pharmacol., 110: 21-30.
603
EFFECTS OF DYNORPHINS ON BODYTEMPERATURE OF RATS E. Cavicchini, S. Candeletti and S. Ferri Institute of Pharmacology. University of Bologna, Irnerio 48, 40126 Bologna ~.~j words
no~ins
-
Bodytemperature
-
Opioid antagonists
-
Verapamil
After the isolation and identification of Dynorphin A (Dyn A) (Goldstein et al.
1979), other
related
to
sequences endowed with opioid
Dyn A,
activity,
have been found to derive from the
structurally-
same precursor,
prodynorphin. The purpose of the present study was to characterize the effects of Dyn A and other prodynorphin-related peptides, namely Dyn B and Dyn A-(1-32), on thermoregulation.
In addition, the involvement of Ca++ in their action was
investigated. Drugs were intracerebroventricularly ( i . c . v . ) administered in unrestrained ninsula,
male rats kept at room temperature (22~C).
San Carlos, CA) and other chemicals injected in a volume of 5 ~ I .
Rectal temperature values were taken 20 min before the tions
Peptides (Pe-
and, after, at
the intervals indicated in
i.c.v,
Figure I.
administraResults were
expressed as mean ~ SEM. Comparisons were made by Student's t - t e s t . (5
Dyn A
and 10 nmol) induced a decrease in body temperature that was maximal
min after within
administration
ana then gradually returned to
120 m i n ; Dyn A-(1-32) (2.5 and 5 nmol) caused a
controi
nmol),
values
longer a c t i v i t y
whereas Dyn B (up to 20 nmol) did not induce any significant The hypothermic effect was prevented by i . c . v ,
30
hypothermia.
administered MR 1452 (30
a preferential antagonist of the ( opioid
receptor.
Naloxone, a
preferential ~ receptor antagonist and naltrexone, its long lasting'analog, up to doses of 100 nmol,as well as MR 1453, (+)-enantiomer of antagonist MR 1452 and devoid of opioid receptors binding properties, the hypothermic effect. mia
did not antagonize
A significant reduction of Dyn A-induced hypother-
(5 pmo]) was elicited by the calcium channel blocker verapamil i.c.v.
administered (10ug). Results of the present investigation showed that i.c.v,
administered Dyn A
and Dyn A-(1-32) induce a clear-cut hypothermia in rats.
0031-6989/881070603-2/$03.00/0
The lack
of
a
© 1988 The Italian Pharmacological Society
Pharmacological Research Communications, Vol. 20, No. 7, 1988
604
1
;
~......L.-L
I
'"
!
.
; ;s so 45 e'o
P
'
io
A
1~0 TIME
Fig. 1. (C) Dyn (A) ( e ) (B) ( e ) (C) ( e ) ~p <
.~
~
'
'"'
; ¢5 ~0 4'5 ~0 AFTER
t.¢.V.
.L.
B
}
.0
INJECTION
1~0
,
,
|
C
f
I
0 15 30 4~ 60
I
so
I
1~0
(mtn)
Effect of the i.c.v, administration of (A) Dyn A, (B) Dyn A-(I-32), B on rectal temperature, in the rat. saline; ( 0 ) Dyn A 2.5 nmol; (BII) Dyn A 5 nmol;(A) Dyn A 10 nmol. saline ; ( 0 ) Dyn A-(1-32) 2.5 nmol; (M) Dyn A-(1-32) 5 nmol; sa|ine; (Z~) Dyn B 10 nmol; (I"I) Dyn B 20 nmoI. 0.05 vs control values.
significant
blockade by naloxone and naltrexone and the finding
that
MR
1452 significantly antagonized the dynorphin-induced hypothermia, indicated a ~ receptor involvement in phenomena elicited by dynorphins. The different efficacy of Dyn A, to
the
Dyn A-(1-32) and Dyn B could be ascribed
different a f f i n i t y of these fragments for the ~ opioid
receptor,
already reported by James et al. (1984), "in vitro". The longer activity of Dyn A-(I-32)
could also
comparison to reduction involvement
of
be related to
a less
Dyn A (Spampinato and Candeletti,
rapid
degradation
1985). Fina]ly
Dyn A-induced hypothermia by verapamil suggested
of Ca++in the peptide effect and supported the
existence
in the an of
relationships between Ca++movements and opioids (Ross et al., 1979). REFERENCES GOLDSTEIN. A., TACHIBANA, S., LOWNEY, L . I . , HUNKAPILLER,M., HOOD, L. (1979), Proc. Natl. Acad. Sci. USA, 76: 6666-66?0. JAMES, I.F., FISCHLI,W. and GOLDSTEIN, A. (1984), J. Pharmacol. Exp. Ther., 228~ 88-93. ROSS, D.H. and CANDENAS, H.L. (1979),Adv. Biochem. Psychopharmacol., 20: 301-336. SPAMPINATO,S. and CANDELETTI, $. (1985),European J. Pharmacol., 110: 21-30.