The antinociceptive effects of histogranin and related peptides in the mouse writhing and tailflick tests: The possible role of central D2 receptor.

Abstract

Histogranin (HN) is an adrenal medullary peptide that was shown to display N-methyl-D-aspartate (NMDA) receptor antagonist activities. Recent data indicated that [Ser1]HN, a stable synthetic analogue of HN, administrated intrathecally (i.t.) can produce significant analgesic effects in rat models of tonic and chronic pain. The aims of the present study were to determine what type(s) of pain HN and related peptides are able to alleviate and which receptor type(s) is(are) involved in such activity. HN and related peptides (intracerebroventricularly: i.c.v.) displayed significant analgesic activity in both the the mouse writhing (visceral type of pain) and tailflick (acute reflex type of pain) assays. The presence of NaCl (10 mM) induced the conversion of the high affinity site into the low affinity site, resulting with an overall Ki of 6.54 +/- 1.2 muM. The relative potencies of HN and related peptides in inhibiting [3H]raclopride binding correlated well with their potencies in inducing analgesic effects in the mouse writhing test (r = 0.86). Our results indicate that HN and related peptides can produce analgesia in thermal and chemical pain assays by a mechanism that involves the participation of the dopamine D2 receptor. (Abstract shortened by UMI.)