Pilocarpine‐Induced Effects on Salivary Secretion as a Pharmacological Biomarker for Cholinergic Parasympathetic Activation

Author(s):  
Nicoline Treijtel ◽  
Dorien Groenendaal‐van de Meent ◽  
Ingrid Michon ◽  
Cees Korstanje ◽  
John Meijer ◽  
...  
Keyword(s):  
2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Baoyu Jia ◽  
Jiachong Liang ◽  
Chunrong Lv ◽  
Sameeullah Memon ◽  
Yi Fang ◽  
...  

AbstractSperm motility is an index tightly associated with male fertility. A close relationship between seminal plasma and sperm motility has been confirmed. This study was to assess the protein and metabolite profiles of seminal plasma obtained from adult goats with high or low sperm motility using the proteomic and metabolomic strategies. In total, 2098 proteins were found. 449 differentially abundant proteins (DAPs) were identified, and 175 DAPs were enriched in the high motility group. The obtained DAPs primarily exist in cytoplasma and extra-cellular portion. The Gene Ontology enrichment analysis demonstrated the main functional roles of these DAPs in regulating biological process, metabolic process of organic substances, cellular-metabolic process, primary-metabolic process, metabolic process of nitrogen compounds, etc. Additionally, the Kyoto-Encyclopedia of Genes and Genomes (KEGG) analysis revealed that these DAPs were primarily involved in phosphatidylinositol signaling system, salivary secretion, proteasome, apoptosis, mitophagy-animal, etc. Aided by the parallel reaction monitoring technology, the abundance changing pattern of 19 selected DAPs was consistent with that of the corresponding proteins obtained by TMT. A total of 4603 metabolites were identified in seminal plasma. 1857 differential metabolites were found between the high motility group and the low motility group, and 999 metabolites were up-regulated in the high motility group. The KEGG analysis demonstrated the primary involvement of the differential metabolites in metabolic and synthetic activities. In conclusion, we first established the proteome and metabolome databank of goat seminal plasma, detecting some proteins and metabolites which may affect sperm motility. This study will be valuable for understanding mechanisms leading to poor sperm motility.


2021 ◽  
Vol 22 (1) ◽  
pp. 404
Author(s):  
Nguyen Khanh Toan ◽  
Nguyen Chi Tai ◽  
Soo-A Kim ◽  
Sang-Gun Ahn

Salivary gland dysfunction induces salivary flow reduction and a dry mouth, and commonly involves oral dysfunction, tooth structure deterioration, and infection through reduced salivation. This study aimed to investigate the impact of aging on the salivary gland by a metabolomics approach in an extensive aging mouse model, SAMP1/Klotho -/- mice. We found that the salivary secretion of SAMP1/Klotho -/- mice was dramatically decreased compared with that of SAMP1/Klotho WT (+/+) mice. Metabolomics profiling analysis showed that the level of acetylcholine was significantly decreased in SAMP1/Klotho -/- mice, although the corresponding levels of acetylcholine precursors, acetyl-CoA and choline, increased. Interestingly, the mRNA and protein expression of choline acetyltransferase (ChAT), which is responsible for catalyzing acetylcholine synthesis, was significantly decreased in SAMP1/Klotho -/- mice. The overexpression of ChAT induced the expression of salivary gland functional markers (α–amylase, ZO-1, and Aqua5) in primary cultured salivary gland cells from SAMP1/Klotho +/+ and -/- mice. In an in vivo study, adeno-associated virus (AAV)-ChAT transduction significantly increased saliva secretion compared with the control in SAMP1/Klotho -/- mice. These results suggest that the dysfunction in acetylcholine biosynthesis induced by ChAT reduction may cause impaired salivary gland function


1922 ◽  
Vol 16 (3) ◽  
pp. 387-389 ◽  
Author(s):  
Clement Nicory
Keyword(s):  

1992 ◽  
Vol 71 (11) ◽  
pp. 1762-1767 ◽  
Author(s):  
M.L. Weaver ◽  
J.M. Tanzer ◽  
P.A. Kramer

We tested whether permucosal delivery of pilocarpine nitrate could be used to elicit significant salivary secretion. Pilocarpine (pKa 6.6 at 37°C) was applied as solutions (pHs 5.6, 6.6, 7.6; 15 mg/mL) to the buccal mucosa (2.8 cm2) of 6 anesthetized dogs. Saliva was collected continuously from cannulated submandibular and parotid ducts and blood sampled during and after drug administration. Plasma pilocarpine levels were determined by reversed-phase HPLC. Absorption rates were determined by use of data from separate zero-order intravenous infusions to the same dogs. Pilocarpine was buccally absorbed at a constant rate of 72.9 ± 38.5 μg/kg/h following its application at pH 7.6. At this pH of the drug solution, the time to appearance of pilocarpine in blood plasma was 0.31 ± 0.08 h, and the time to appearance of salivary flow was 0.86 ± 0.32 h. A threshold dose of 32.9 ± 7.5 ug/kg was required to induce secretion with the pH 7.6 drug, the steady-state plasma concentration was 28.9 ± 19.3 ng/mL, and the steady-state submandibular flow rate was 0.14 ± 0.11 mL/ min/gland pair. Salivary flow induction was symmetrical and reached levels as high as 0.35 mL/min/submandibular gland pair without apparent tachyphylaxis. Results at pHs 5.6, 6.6, and 7.6 were consistent with the hypothesis that pilocarpine is primarily absorbed as un-ionized drug. The data indicate that transmucosal delivery of pilocarpine, avoiding "first pass" hepatic loss, may hold promise for the treatment of xerostomia.


2010 ◽  
Vol 120 (5) ◽  
pp. 355-360 ◽  
Author(s):  
Tetsuo Kawasaka ◽  
Megumi Shimodozono ◽  
Atsuko Ogata ◽  
Nobuyuki Tanaka ◽  
Kazumi Kawahira

2021 ◽  
Author(s):  
Baoyu Jia ◽  
Jiangchong Liang ◽  
Chunrong Lv ◽  
Sameeullah Memon ◽  
Yi Fang ◽  
...  

Abstract Sperm motility is an index tightly associated with male fertility. A close relationship between seminal plasma and sperm motility has been confirmed. This study was to assess the protein and metabolite profiles of seminal plasma obtained from adult goats with high or low sperm motility using the proteomic and metabolomic strategies. In total, 2098 proteins were found. 449 differentially expressed proteins (DEPs) were identified, and 175 DEPs were enriched in the high motility group. The obtained DEPs primarily exist in cytoplasma and extra-cellular portion. The Gene Ontology enrichment analysis demonstrated the main functional roles of these DEPs in regulating biological process, metabolic process of organic substances, cellular-metabolic process, primary-metabolic process, metabolic process of nitrogen compounds, etc. Additionally, the Kyoto-Encyclopedia of Genes and Genomes (KEGG) analysis revealed that these DEPs were primarily involved in phosphatidylinositol signaling system, salivary secretion, proteasome, apoptosis, mitophagy-animal, etc. Aided by the parallel reaction monitoring technology, the abundance changing pattern of 19 selected DEPs was consistent with that of the corresponding proteins obtained by TMT. A total of 4603 metabolites were identified in seminal plasma. 1857 differential metabolites were found between the high motility group and the low motility group, and 999 metabolites were up-regulated in the high motility group. The KEGG analysis demonstrated the primary involvement of the differential metabolites in metabolic and synthetic activities. In conclusion, we first established the proteome and metabolome databank of goat seminal plasma, detecting some proteins and metabolites which may affect sperm motility. This study will be valuable for understanding mechanisms leading to poor sperm motility.


1987 ◽  
Vol 66 (1_suppl) ◽  
pp. 628-632 ◽  
Author(s):  
B. J. Baum

It is very well established that the principal control of salivary secretion is derived from autonomic innervation. Transmission of a neural signal to a salivary gland acinar cell occurs chemically via neurotransmitters, the first messengers of a secretory response. Neurotransmitters bind to specific cell surface receptor proteins, an event which activates precise transduction mechanisms which then transfer the neural signal to the inside of the cell. There are two major transduction mechanisms operative in salivary gland acinar cells. One involves the generation of cAMP, the other involves the breakdown of plasma membrane polyphosphoinositides. For both mechanisms, the appropriate stimulated receptor activates a second plasma membrane protein, termed an N (or G) protein. The N protein requires GTP to activate an enzyme (adenylate cyclase or phospholipase C), which then catalyzes the formation of a second messenger (cAMP and inositol trisphosphatel diacylglyeerol, respectively). This action provides the intracellular signal for secretory events (protein, fluid, electrolyte secretion) to begin.


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