Physiological cAMP-elevating secretagogues differentially regulate fluid and protein secretions in mouse submandibular and sublingual glands

• Published in: American Journal of Physiology: Cell Physiology 2019-05, Vol.316 (5), p.C690-C697
• Main Authors: Kondo, Yusuke, Melvin, James E, Catalan, Marcelo A
• Format: Article
• Language: English
• Subjects: Acetylcholine receptors (muscarinic); Acute effects; Animals; Calcium; Carbachol; Carbachol - pharmacology; Colforsin - pharmacology; Cyclic AMP; Cyclic AMP - agonists; Cyclic AMP - metabolism; Epithelial cells; Exocrine glands; Forskolin; G protein-coupled receptors; Innervation; Intestine; Isoproterenol; Mice; Mice, 129 Strain; Organ Culture Techniques; Parasympathetic nervous system; Peptides; Perfusion; Protein composition; Proteins; Saliva; Saliva - drug effects; Saliva - metabolism; Salivary gland; Secretagogues - pharmacology; Secretions; Sodium chloride; Sublingual Gland - drug effects; Sublingual Gland - metabolism; Submandibular Gland - drug effects; Submandibular Gland - metabolism; Sympathomimetics; Vasoactive agents; Vasoactive intestinal peptide
• ISSN: 0363-6143; 1522-1563
• DOI: 10.1152/ajpcell.00421.2018

The mechanisms underlying the functional differences in sympathetic and parasympathetic regulation of the major salivary glands have received little attention. The acute effects of parasympathetic muscarinic (carbachol)-dependent and combined parasympathetic-dependent plus cAMP-dependent pathways on fluid secretion rates, ion composition, and protein content were assessed using a newly developed ex vivo preparation that allows the simultaneous perfusion of the mouse submandibular (SMGs) and sublingual glands (SLGs). Our results confirm that the muscarinic-dependent pathway accounts for the bulk of salivation in SMGs and SLGs, whereas costimulation with a cAMP-increasing agent (forskolin, isoproterenol, or vasoactive intestinal peptide) did not increase the flow rate. Costimulation with carbachol plus the β-adrenergic agonist isoproterenol decreased the concentration of NaCl and produced a substantial increase in the protein and Ca content of SMG but not SLG saliva, consistent with a sparse sympathetic innervation of the SLGs. On the other hand, forskolin, which bypasses receptors to increase intracellular cAMP by directly activating the enzyme adenylate cyclase, enhanced the secretion of protein and Ca by both the SMGs and SLGs. In contrast, isoproterenol and vasoactive intestinal peptide specifically stimulated protein secretion in SMG and SLG salivas, respectively. In summary, cAMP-dependent signaling does not play a major role in the stimulation of fluid secretion in SMGs and SLGs, whereas each cAMP-increasing agonist behaves differently in a gland-specific manner suggesting differential expression of G protein-coupled receptors in the epithelial cells of SMGs and SLGs.