Hypothermia elicited by some prodynorphin-derived peptides: opioid and non-opioid actions.
Prodynorphin-derived peptides were tested for their effects on body temperature after intracerebroventricular administration to unrestrained male rats. Dynorphin A (Dyn A) (5 and 10 nmol) and Dynorphin A-(1-32) (Dyn A-(1-32) (2.5 and 5 nmol) lowered body temperature with a maximum approximately 30 min after administration. Dyn B (up to 50 nmol) did not induce hypothermia. Lower doses of all peptides did not alter body temperature. The hypothermic effect was significantly, but not completely prevented by MR1452 (30 nmol), a preferential antagonist of the kappa receptor, administered intracerebroventricularly. Naloxone, a mu receptor antagonist, naltrexone, its long acting analog up to doses of 100 nmol, as well as MR1453, the (+)-enantiomer of kappa antagonist MR1452 with no opioid binding properties, did not prevent the hypothermic effect. Moreover, episodic barrel rolling and bizarre postures elicited by Dyn A and Dyn A-(1-32) were reduced in rats pretreated i.c.v. with MR1452 (30 nmol), but not with naloxone (up to 100 nmol). Interestingly, des-Tyr-Dynorphin A (Dyn A-(2-17)), a fragment with virtually no opioid binding potential, was 4 times less potent that Dyn A in inducing hypothermia. These findings are consistent with the hypothesis that prodynorphin-derived peptides effects are not exclusively opioids in nature.
Cavicchini
E
E
Institute of Pharmacology, University of Bologna, Italy.
Candeletti
S
S
Spampinato
S
S
Ferri
S
S
D000818:Animals; D001575:Benzomorphans / Q000494:pharmacology; D001831:Body Temperature; D004399:Dynorphins / Q000031:analogs & derivatives* / Q000494:pharmacology*; D004723:Endorphins / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D007035:Hypothermia / Q000139:chemically induced*; D007700:Kinetics; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D009270:Naloxone / Q000494:pharmacology; D009271:Naltrexone / Q000494:pharmacology; D010446:Peptide Fragments / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011957:Receptors, Opioid / Q000378:metabolism*
D001575:Benzomorphans; D004723:Endorphins; D010446:Peptide Fragments; D011957:Receptors, Opioid; D009270:Naloxone; D009271:Naltrexone; C029552:Mr 1452; D004399:Dynorphins; C045485:dynorphin (1-32); C036200:rimorphin; C082245:dynorphin (2-17)