Intracellular signal transduction systems induced by rat neurotensin NT2 receptor expressed in CHO cells

S88

085

IN

VNO

SIGNAL

NOCICEPTIN

H. UEDA’, M. INOUE’,

RECEEOR

OF

OR SUBSTANCE

S. TOKUYAMA’, A. YOSHIDA’,

‘Dept. of Mol. Pharmacol.

& Neurosci.,

Nagasaki

Univ.,

PERIPHERALLY-ORIGINAIED

NOCICEPTION

IN

P K/O MICE.

H. lXESHIMA’,

A. ZIMMER3

Sch. of Pharmac.

Sci., Nagasaki

852-8521,

Japan.

“Dept. of

Facult. of Med., The Univ. of Tokyo, Tokyo 113-0033, Japan. 3Sect. of Genetics, NIMH, MD 20892, U.S.A.

Pharmacol.,

In in vivo reconstitution found to be coupled intraplantarly

experiments

caused a nociceptive

trisphosphate

using baculovirus/SQl

cell expression

system,

the Nociceptin

to G,, and G,,, but not G,, Gu nor G 12 In m VIVO peripheral

abolished by local applications

flexor reflex lOOO-fold as potent as substance

of NKI

antagonist,

(InsPs) receptor antagonist,

in Noci-receptor

knockout

Noci produced

nociceptive

086

pertussis

toxin-treatment,

EGTA or tetrodotoxin,

responses

(pain)

through

and SP release from the peripheral

The responses

C (PLC) inhibitor,

YAMADAl,

IDept. of Psychiatry,

MISA YAMADA2,

inositol

gene All these findings suggest that

using G,, PLC, InsP3-receptor-gated

Cazt influx

nerve endings.

ALAIN LOMBET3,

Sch. of Med., Showa Univ., Shinagawa-ku,

Sci., Showa Univ., Shinagawa-ku,

were

In addition they were not observed

INTRACELLULAR SIGNAL TRANSDUCTION SYSTEMS INDUCED NEUROTENSIN NT2 RECEPTOR EXPRESSED IN CHO CELLS

MITSUHIKO

was

analgesic test in mice, Noci given

phospholipase

of tachykininl

the mechanisms

(Noci) receptor

P (SP) or bradykinin.

but not thapsigargin

mice nor in mice with targeted disruption

through the plasma membranes

maccutical

IRANSDUCTION

PATRICIA

FORGEZ3,

BY RAT

WILLIAM

ROStiNE3

Tokyo 142-8666, 2Dept. of Pharmacology,

Tokyo 142-8555, 31NSERM U339, Hopital Saint-Antoine,

Sch. of Phar-

Paris 75012

Several of pharmacological effects induced by neurotensin are mediated by a high-affinity neurotensin NT1 receptor. On the other hand, a low-affinity levocabastine-sensitive neurotensin NT2 receptor was molecularly cloned from rat brain. In this study, in contrast to NT1 receptor, SR48692 (an antagonist for NT1 receptor) strongly stimulated intracellular Ca” mobilization in transfected Chinese hamster ovary cells expressing rat NT2 receptor, thus acting as potent NT2 receptor agonist. Furthermore, despite of their affinities for NT2 receptor, the Ca” responses to NT1 agonists, neurotensin and related analogue of neurotensin, were much smaller than that observed with SR48692. Additionally, neurotensin and related peptide-agonists did not stimulate PI hydrolysis and CAMP formation. Our findings demonstrated that NT1 and NT2 receptors present distinct functional characteristics.

087

ANALYSIS MICE.

OF NEUROMEDIN

HIROKO 0HKI-HAMAZAKI’,2, KEIJI WADA

YASUSHI

B RECEPTOR

SAKAI’,

FUNCTION

KATSUO

BY USlNG THE NMB-R-DEFICIENT

KAMATA4, KEI WATASE2, KAZUYUKI

YAMADA2,

‘Dept. of Neurochem., Tokyo Inst. of Psychiatry, Setagaya-ku, Tokyo 156-8585, 2Dept. of Degener. Neural. Dis., Nat]. Inst. of Neurosci., NCNP, Kodaira-city, Tokyo 187-8502, ‘Dept. of Physiol., Showa Univ. College of Med. Sci., Midori-ku, Yokohama-city, Kanagawa 226-8555, “Dept. of Physiol. and Morphol., Inst. of Med. Chem., Hoshi Univ., Shinagawa-ku, Tokyo 142-0063. Receptors

for bombesin-like

receptor

(GRP-R)

deficient

or BRS-3-deficient

peptides

and bombesin

in mammals

receptor

mice. To further investigate

lacking NMB-R. Using these mice, we evaluated muscle contraction functions

include

subtype-3

neuromedin

(BRS-3).

B receptor

We have already

the functional

properties

and food intake) and behavior

(activity

and social behavior).

gastrin-releasing

peptide

and characterized

GRP-R-

of each receptor, we also generated

the role of NMB-R in physiological

of these receptors are only partially overlapped,

(NMB-R), generated functions

(thermoregulation,

The results provide

but rather they have proper function, respectively.

evidence

mice

smooth that the