We have studied the effects of glutamate receptor agonists on the cyto
solic Ca2+ concentration ([Ca2+](i)) of single rat anterior pituitary
(AP) cells, Ionotropic (NMDA and kainate/AMPA) and, to a smaller exten
t, metabotropic glutamate receptors were both present in all the five
AP cell types, defined by the hormone they store, Cells within all the
types responded also to thyrotropin-releasing hormone (TRH). Alternat
ive typing by the response to four well-established hypothalamic relea
sing hormones (HRHs), GHRH, GnRH, CRH, and TRH, was performed, One-thi
rd of the cells were not sensitive to any HRH, another third were sens
itive to only one HRH, and the last third were sensitive to more than
one HRH, frequently to all four, Only the cells responding to TRH show
ed functional glutamate receptors, Superimposed to the above associati
on, the strongest responses to glutamate were found in the cells respo
nsive to multiple HRHs, These results suggest that glutamate may act,
by a nonsynaptic mechanism, as a new releasing factor for one or, like
TRH, several AIP hormones, Coexpression of glutamate and TRH receptor
s in the subpopulation of cells responsive to multiple HRHs might have
a functional meaning, perhaps related to phenotypic plasticity and lo
ng-term regulation of hormone secretion by the anterior pituitary.