High level of accumulation of a mRNA coding for a precursor-like protein in the submaxillary gland of male rats.

Rosinski‐Chupin, Isabelle; Tronik, Diana; Rougeon, François

doi:10.1073/pnas.85.22.8553

Cited by 48 publications

(38 citation statements)

References 37 publications

(32 reference statements)

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“…in the SMG is regulated by androgens [23], which are present in rats from the fourth postnatal week onwards, it was of interest to determine the pentapeptide-immunoreactive content in the male rat SMG of different postnatal ages. In related experiments, using 14-week-old male and female rats, the effect of sexual difference was also assessed.…”

Section: Concentrations and Molecular Forms Of Pentapeptide-related Pmentioning

confidence: 99%

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Selective processing of submandibular rat 1 protein at dibasic cleavage sites

Rougeot

Rosinski‐Chupin

Njamkepo

et al. 1994

European Journal of Biochemistry

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The amino acid sequence of submandibular rat 1 (SMR1) protein, deduced from its cDNA sequence, led to the prediction that the SMR1 gene encodes a hormone‐like precursor [Rosinski‐Chupin, I., Tronik, D. & Rougeon, F. (1988) Proc. Natl Acad. Sci. USA 85, 8553–8557]. SMR1 contains an N‐terminal putative secretory signal sequence and a tetrapeptide (QHNP), located between dibasic amino acids which constitute the most common signal for prohormone processing. We have isolated and characterized from the male rat submandibular gland and its secretions three structurally related peptides, namely an undecapeptide (VRGPRRQHNPR), a hexapeptide (RQHNPR) and a pentapeptide (QHNPR) generated from SMR1 by selective proteolytic cleavages at pairs of arginine residues. The biosynthesis of these peptides is subjected to distinct regulatory pathways depending on the organ, sex and age of the rat. Furthermore, the peptides are differentially distributed in the submandibular gland and in resting or epinephrine‐elicited submandibular salivary secretions, suggesting distinct proteolytic pathways for their maturation. The undecapeptide is generated in the gland of both male and female rats, but under basal conditions it is only released into the saliva in male animals. The hexapeptide is produced in large amounts in the gland of adult male rats and released into the saliva in both resting and stimulated conditions. The pentapeptide appears only in the male saliva and is present mostly under stimulated conditions. In addition, administration of epinephrine induces the release of the hexapeptide from the submandibular gland into the bloodstream. The evidence indicates that the rat submandibular gland can function as a dual exocrine and endocrine organ for the SMR1‐derived hexapeptide, as has been reported for nerve growth factor, epidermal growth factor, renin and kallikrein. Although the biological activities of the SMR1‐derived peptides are not yet known, their high production and adrenergic‐induced release only into the saliva and bloodstream of adult male rats, suggest a physiological involvement in some male‐specific processes.

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Section: Concentrations and Molecular Forms Of Pentapeptide-related Pmentioning

confidence: 99%

“…A major rat-specific mRNA, which accumulates in the SMG in response to androgens, has been characterized by Rosinski-Chupin et al [23,241. This mRNA is expressed in a highly tissue-specific manner and is 1000-3000-fold more abundant in male than in female rats.…”

mentioning

confidence: 99%

Selective processing of submandibular rat 1 protein at dibasic cleavage sites

Rougeot

Rosinski‐Chupin

Njamkepo

et al. 1994

European Journal of Biochemistry

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“…Glyoxal-denatured RNA (100 g) was resolved by electrophoresis in a 1.1% agarose gel (Gründemann and Koepsell 1994) and blotted on Hybond N membrane (Amersham; Arlington Heights, IL) as described (Chomczynski 1992). For analysis of androgen regulation, RNAs were prepared and analyzed as previously described (Rosinski-Chupin et al 1988). For each group of animals, five individual preparations of RNA were pooled and analyzed.…”

Section: Northern Blot Analysismentioning

confidence: 99%

“…As a consequence, the VCS family encodes proteins that are very diverse in amino acid content, structure, and probably function. The first gene of this family to be described was the rat VCSA1 gene, which is expressed mainly in SMG and encodes the SMR1 protein (Rosinski-Chupin et al 1988). SMR1 is a prohormone protein, whose maturation generates three related peptides, which are released into the saliva and bloodstream (Rougeot et al 1994).…”

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confidence: 99%

Acinar Cells Are Target Cells for Androgens in Mouse Submandibular Glands

Señorale-Pose

Jacqueson

Rougeon

et al. 1998

J Histochem Cytochem.

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S U M M A R YThe variable coding sequence (VCS) multigene family encodes diverse salivary proteins, such as the SMR1 prohormone and the PR-VB1 proline-rich protein in the rat. In situ hybridization was used to study the cell-specific expression of two new mouse VCS genes, Vcs1 and Vcs2. We show that the Vcs1 transcripts, which code for a proline-rich protein, MSG1, are highly abundant in male and female parotid glands, in which they are specifically detected in acinar cells. No expression was seen in the submandibular or sublingual glands. In contrast, Vcs2 transcripts were found only in the acinar cells of the submandibular glands (SMGs) of male mice, in which they are expressed in response to androgens. Expression was found to be heterogeneous within acinar structures. No Vcs2 transcripts were detected in the SMGs of females or castrated males by Northern blot, RNase protection, or in situ hybridization. Androgen administration to females or castrated males induced expression at a level comparable to that of intact males. The Vcs2 gene is the first example of a mouse androgen-regulated gene that is expressed in SMG acinar cells. This result, in addition to our previous observation on SMR1 expression in rats, demonstrates that both acinar cells and granular convoluted tubule (GCT) cells are target cells for androgen action in rodent SMG. (J Histochem Cytochem 46:669-678, 1998)

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“…In a genomic approach, an androgen-regulated gene has been identified, which is predominantly expressed in the submandibular gland and prostate of adult rats (6,7). The gene encodes a precursor protein, submandibular rat 1 protein (SMR 1 ), which gives rise to three structurally related peptides: SMR 1 -undecapeptide, SMR 1 -hexapeptide, and SMR 1 -pentapeptide.…”

mentioning

confidence: 99%

Sialorphin, a natural inhibitor of rat membrane-bound neutral endopeptidase that displays analgesic activity

Rougeot

Messaoudi

Hermitte

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

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Sialorphin is an exocrine and endocrine signaling mediator, which has been identified by a genomic approach. It is synthesized predominantly in the submandibular gland and prostate of adult rats in response to androgen steroids and is released locally and systemically in response to stress. We now demonstrate that the cell surface molecule to which sialorphin binds in vivo in the rat kidney is the membrane-anchored neutral endopeptidase (neprilysin; NEP, EC 3.4.24.11). NEP plays an important role in nervous and peripheral tissues, as it turns off several peptide-signaling events at the cell surface. We show that sialorphin prevents spinal and renal NEP from breaking down its two physiologically relevant substrates, substance P and Met-enkephalin in vitro. Sialorphin inhibited the breakdown of substance P with an IC50 of 0.4 -1 M and behaved as a competitive inhibitor. In vivo, i.v. sialorphin elicited potent antinociceptive responses in two behavioral rat models of injury-induced acute and tonic pain, the pin-pain test and formalin test. The analgesia induced by 100 -200 g͞kg doses of sialorphin required the activation of -and ␦-opioid receptors, consistent with the involvement of endogenous opioid receptors in enkephalinergic transmission. We conclude that sialorphin protects endogenous enkephalins released after nociceptive stimuli by inhibiting NEP in vivo. Sialorphin is a natural systemically active regulator of NEP activity. Furthermore, our study provides evidence that it is a physiological modulator of pain perception after injury and might be the progenitor of a new class of therapeutic molecules.

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High level of accumulation of a mRNA coding for a precursor-like protein in the submaxillary gland of male rats.

Cited by 48 publications

References 37 publications

Selective processing of submandibular rat 1 protein at dibasic cleavage sites

Selective processing of submandibular rat 1 protein at dibasic cleavage sites

Acinar Cells Are Target Cells for Androgens in Mouse Submandibular Glands

Sialorphin, a natural inhibitor of rat membrane-bound neutral endopeptidase that displays analgesic activity

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