cAMP and cGMP in nasal mucus: relationships to taste and smell dysfunction, gender and age

Abstract

Clin Invest Med 2008; 31 (2): E71-E77. AbstractPurpose: To evaluate the presence and concentration of cAMP and cGMP in human nasal mucus in normal volunteers, to relate these findings to age and gender, and to compare normal levels with those in patients with taste and smell dysfunction. Methods: Nasal mucus was collected over one to four days in 66 normal subjects and 203 patients with smell loss (hyposmia). Samples were centrifuged at 20,000 rpm, the supernatant removed and analyzed for cAMP and cGMP by using a 96 plate technique with a specific spectrophotometric colorimetric ELISA assay. Results: Both cAMP and cGMP were present in human nasal mucus with both cAMP and cGMP significantly higher in normal women than in normal men [men vs. women; cAMP, 0.23±0.002 vs. 0.34±0.05 (P<0.05); cGMP, 0.28±0.03 vs. 0.63±0.12 (P<0.01)].Both cAMP and cGMP changed with age; both moieties increased in a U shaped, parabolic pattern reaching a peak at age 41-50 with cAMP diminishing thereafter and then increasing to its highest level over age 70. Both cAMP and cGMP were lower in patients with taste and smell dysfunction than in normal subjects [normals vs. patients; cAMP, 0.31±0.05 vs. 0.15±0.02 (P<0.01); cGMP, 0.56±0.07 vs. 0.025±0.02 (P<0.001)] suggesting a relationship to olfactory pathology. Conclusions: This is the first definitive study to demonstrate the presence of these cyclic nucleotides in nasal mucus and the first to reveal decreased levels in patients with impaired taste and smell function. Since olfactory receptor

Sonic Hedgehog in Nasal Mucus is a Biomarker for Smell Loss in Patients with Hyposmia

“…However, there are many moieties in nasal mucus in humans not identified through these and other analyses [13]. Chief among these are adenylyl cyclases [14,15] and their downstream metabolites cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) [16,17]. These latter moieties were found decreased in hyposmic patients compared to normal subjects [16,17].…”

“…Chief among these are adenylyl cyclases [14,15] and their downstream metabolites cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) [16,17]. These latter moieties were found decreased in hyposmic patients compared to normal subjects [16,17]. Sonic hedgehog (Shh) has been characterized as a critical factor in cellular growth and development of taste receptors [18,19] with its absence associated with inhibition of growth and development of receptors of these sensory organs [20]; however, it has not been identified to play a role in olfaction per se.…”

Intranasal Theophylline Treatment of Hyposmia and Hypogeusia

“…Each patient had undergone previous evaluation before any drug treatment, 12,13 followed by treatment with oral theophylline. These patients had hyposmia and hypogeusia and exhibited levels of cAMP and cGMP lower than their respective reference ranges in the saliva 35,36 and nasal mucus 37,38 before theophylline treatment. These 10 patients were selected from the group undergoing previous evaluation and treatment for the intranasal trial because (1) their response to oral theophylline was subjectively submaximal; (2) they developed adverse effects after attempts to increase the drug dose to obtain a more maximal clinical response, thus limiting the administered drug dose; and (3) they resided in an area in close proximity to The Clinic, which made their frequent return visits to The Clinic more practical for any additional clinical trial.…”

“…33 Effective treatment to increase secretion of these growth factors is therefore necessary to improve hypogeusia and hyposmia 5,12,13 and return taste and smell function to normal as demonstrated by several previous studies. 5,12,13 To understand more about these processes, a comprehensive study of many patients with loss of smell and taste determined that levels of the salivary 34,35 and nasal mucus 36,37 growth factors cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) were lower than in healthy subjects and were responsible for the onset of hyposmia and hypogeusia in many of these patients. 38,39 Indeed, as hyposmia increased in severity, levels of these salivary 35 and nasal mucus 37 growth factors decreased in a consistent manner.…”

“…With assistance of an established pharmaceutical company, the drug was packaged for sterile, intranasal delivery. Using this device, an open-label, singlesource, controlled pilot study in 10 patients with hyposmia and hypogeusia and with levels of parotid saliva 35,36 and nasal mucus 37,38 cAMP and cGMP below the reference range was performed to determine safety and to compare smell and taste responses after intranasal theophylline treatment, with patient responses before any treatment and after oral theophylline treatment.…”