The G protein-coupled receptor kinase type 4 mediates the homologous desens
itisation of type-1 metabotropic glutamate (mGlu1) receptors and is predomi
nantly expressed in the testis. Hence, we searched for the expression of mG
lu1 or other mGlu receptor subtypes in rat and human testes. RT-PCR analysi
s showed the presence of mGlu1, -4 and -5 (but not -2 or -3) receptor mRNA
in the rat testis. The presence of mGlu1 and -5 (but not mGlu2/3) receptor
proteins was also demonstrated by Western blot analysis. In the rat testis,
both mGlu1a and -5 receptors were highly expressed in cells of the germina
l line. It is likely that these receptors are functional, because the agoni
st, (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid, was able to stimulat
e inositol phospholipid hydrolysis in slices prepared from rat testes. Immu
nocytochemical analysis of bioptic samples from human testes showed a high
expression of mGlu5 receptors inside the seminiferous tubuli, whereas mGlu1
a immunoreactivity was restricted to intertubular spaces. mGlu5 receptors w
ere also present in mature spermatozoa, where they were localised in the mi
d-piece and tail. This localisation coincided with that of beta -arrestin,
a protein that is critically involved in the homologous desensitisation and
internalisation of G protein-coupled receptors. Taken collectively, these
results offer the first evidence for the expression of any glutamate recept
or in testes, and suggest that at least mGlu5 receptors are present and fun
ctionally active in mature human sperm.