Secretagogue-coupled changes in the expression of glutamine/glutamic acid-rich proteins (GRPs). Isoproterenol induces changes in GRP transcript expression and changes in isoforms secreted

Abstract

Glutamine/glutamic-acid rich proteins (GRPs) are a family of rat submandibular gland acinar proteins which are secreted in response to beta-adrenergic agonists such as isoproterenol. Two forms of GRP transcripts have been identified by isolating plasmids containing cDNAs which code for two distinct GRPs, termed GRP-Ca and GRP-Cb. GRP-Ca and GRP-Cb have identical sequences up to nucleotide 670. This is followed by a unique 90- (GRP-Ca) or 95- (GRP-Cb) base pair element. Both forms have common 3' nucleotide sequences, although the GRP-Cb stop codon is 27 base pairs further 3' from the start site of transcription. Systemic exposure to isoproterenol results in a decrease in the relative steady-state level of GRP-Ca transcripts within 24 h, whereas GRP-Cb message increases after several days of isoproterenol treatment. The demonstration that secretagogues such as isoproterenol can modulate changes in salivary protein expression suggests that the machinery responsible for exocytosis is functionally coupled to the cellular apparatus involved in acinar protein production.