Functional evidence for the existence of three tachykinin receptor subtypes in the rat central nervous system

Pharmaco~gicalReseamhCommun~ation~Vo~2~ Supp~mentl~ 1988

230

FUNCTIONAL EVIDENCE FO~ THE EXISTENCE OF THREE TACHYKININ RECEPTOR SUBTYPES IN THE RAT CENTRAL NERVOUS SYSTEM M. Massi, M. Perfumi, C. Polidori, L. Gentili and G. de Caro Institute of Pharmacology, University of Camerino

Key words: Tachykinin receptors, salt appetite, water intake.

Multiple

tachy~inins

(TKs)

occur

both

in

peripheral

organs

and

in

the central nervous system (CNS) of the rat. Accordingly, 3 TK receptor subtypes

i~ave been

respectively considered

proposed:

s~bstance P the

the

NK-I,

the

(SP), neurokinin A

endogenous

ligands

(Buch

NK~2

and

NK-3,

(NKA)

and

neurokinin B are

and

Burcher,

functional evidence for the 3 receptors has been so

for which

1986). However,

far provided only

for peripheral effects of TKs. We

now report

Na depletion,

that in 3 behavioural tests

(salt

intake elicited by

water intake induced by subcutaneous hypertonic NaCI and

angiotensin II-induced drinking) the rank order of potency of TKs, injected

intracerebroventricularly,

suggests

the

involvement

of

3

receptor

subtypes similar to the peripheral ones. Salt

intake in Na depleted rats is potently inhibited

by NK-3 ago-

nists, while NKA and SP are only weak inhibitors. Water intake following subcutaneous hypertonic NaC1 is markediy suppressed

by NK-2 agonists,

while NK-I agonists are weak inhibitors and

NK-3 agonists are almost completely ineffective. Drinking induced

by central injection of angiotensin II is inhibited

by NK-I agonists, but not by NK-2 and NK-3 agonists. Present

findings

provide

functional

evidence

for

the

existence

of

3 TK receptor subtypes in the-rat CNS and propose the validity of these tests to evaluate receptor selectivjby of new synthetic TKs.

REFERENCES: Buch S.H and Burcher E. (1986) Trends Pharmacol.Sci.7:437-438.