EVIDENCE FOR ADDITIONAL NEUROTENSIN RECEPTOR SUBTYPES - NEUROTENSIN ANALOGS THAT DISTINGUISH BETWEEN NEUROTENSIN-MEDIATED HYPOTHERMIA AND ANTINOCICEPTION

Neurotensin (NT), a tridecapeptide, is a neurotransmitter that elicits potent effects including hypothermia and antinociception in mice and rats. To date, there are two types of the neurotensin receptor (NTR) t hat have been molecularly cloned from the rat. However, several lines of evidence suggest the presence of additional NTR subtypes. We have i dentified a NT analog of the NT(8-13) fragment, NT27, that selectively causes only the hypothermic response in vivo, when microinjected into the periaqueductal gray (PAG) of rats. A dose of 18 nmol of NT or NT2 7 caused a body temperature lowering of 1.8 and 1.2 degrees C, respect ively. This same dose of NT or NT27 yielded a hotplate maximum physiol ogical effect of 75% and 25%, respectively. Interestingly, despite its high K-D (620 nM) at the cloned NTR-1, NT27-I (the iodinated form of NT27) exerted a potent hypothermic effect even at a very low dose (0.6 nmol). Equally intriguing, was that NT24, a sterioisomer of NT27, wit h a much higher affinity (K-D = 0.5 nM) at NTR-1, did not selectively induce hypothermia in mice, but did selectively induce hypothermia in rats. (C) 1998 Elsevier Science B.V.