Abstract
Parotid salivary levels of cyclic adenosine monophosphate (cAMP) have been previously
demonstrated to be lower than normal in patients with taste and smell dysfunction.
To define these results more fully, we analyzed parotid salivary levels of cAMP and
cyclic guanosine monophosphate (cGMP) with respect to severity of smell loss in these
patients. Smell loss severity was defined by psychophysical measurements of olfactory function and classified into
4 types from most severe to least severe loss. This resulted in patients exhibiting,
in order of loss severity (from greatest to least), anosmia > type I hyposmia > type
II hyposmia > type III hyposmia. Parotid saliva cAMP and cGMP were measured independently
using a sensitive spectrophotometric 96-plate enzyme-linked immunosorbent assay technique;
mean levels were categorized by clinical classification of loss severity. As smell
loss severity decreased, salivary cAMP and cGMP levels increased consistently with
each stepwise change of clinical loss severity. This is the first demonstration of
biochemical changes in saliva associated with a quantitative classification of smell
loss. These results reflect a biochemical method to identify and classify patients
with smell loss in some respects similar to initial typing of serum lipid levels to
assist in risk classification of patients with cardiovascular disease.
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to Metabolism - Clinical and ExperimentalAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- Possible novel mechanism for bitter taste mediated through cGMP.J Neurophysiol. 1999; 81: 1661-1665
- High activity of adenylyl cyclase in olfactory and gustatory organs.Biochem Biophys Res Comm. 1972; 48: 30-34
- Odorant-sensitive adenylate cyclase may mediate olfactory reception.Nature. 1985; 316: 255-258
- Molecular neurobiology of olfaction.Crit Rev Neurobiol. 1993; 7: 1-22
- Single odor-sensitive channels in olfactory receptor neurons are also gated by cyclic nucleotides.J Neurosci. 1991; 11: 3565-3572
- Regulation of intracellular cyclic GMP levels in olfactory sensory neurons.J Neurochem. 2005; 95: 200-209
- Aberrant signaling in the olfactory system: a mechanism for smell loss.FASEB J. 2004; 18: A1198
- cAMP and cGMP in human parotid saliva: relationship to taste and smell dysfunction, gender and age.Am J Med Sci. 2007; 334: 431-440
- The definition of primary and accessory areas of olfaction as the basis for a classification of decreased olfactory acuity.in: Hayashi T. Olfaction and taste II. Pergamon Press, London1967: 235-252
- Concepts of therapy in taste and smell dysfunction: repair of sensory receptor function as primary treatment.in: Kurihara K. Suzuki N. Ogawa H. Olfaction and taste XI. Springer Verlag, New York1994: 568-573
- Taste and smell disorders, human.in: Adelman G. Smith B.H. Encyclopedia of neuroscience. 3rd ed. Birkhauser, Boston2004
- cAMP and cGMP in nasal mucus: relationships to taste and smell dysfunction, gender and age.Clin Invest Med. 2008; 31: E71-E77
- cAMP and cGMP in nasal mucus related to severity of smell loss in patients with smell dysfunction.Clin Invest Med. 2008; 31: E78-E84
- Evaluation and treatment of human olfactory dysfunction.in: English G.M. Otolaryngology. vol 2. Lippincott, Philadelphia1993: 1-86
- A zinc protein isolated from human parotid saliva.Proc Natl Acad Sci USA. 1975; 72: 488-492
R&D Systems. cAMP kit. Minneapolis, MN. Cyclic AMP (low pH) immunoassay. Catalog number DE0355.
R&D Systems, Minneapolis, MN. Cyclic GMP (low pH) immunoassay. Catalog number DE0550.
- A double blind study of the effects of zinc sulfate on taste and smell dysfunction.Am J Med Sci. 1976; 272: 285-299
- Handbook of psychology.Wiley, New York1951
- Hyposmia secondary to excision of the olfactory epithelium. The definition of primary and accessory areas of olfaction.Life Sci. 1966; 5: 331-334
- Complete anosmia—the absence of olfaction at primary and accessory olfactory areas.Life Sci. 1966; 3: 1031-1040
- Hyposmia after paranasal sinus exenteration or laryngectomy.Am J Surg. 1970; 120: 485-491
- Hyposmia following laryngectomy.Lancet. 1968; II: 479-487
- On the mechanism of hyposmia following laryngectomy in man.Laryngoscope. 1972; 82: 836-843
- Measurement standards of smell acuity are necessary to define pathology and treatment of smell loss.FASEB J. 2006; 20: A380
- Neuronal cyclic AMP controls the developmental loss in ability of axons to regenerate.J Neurosci. 2001; 21: 4731-4739
- A protein kinase A–dependent molecular switch in synapsins regulates neurite outgrowth.Nat Neurosci. 2002; 8: 431-437
- The biology and mechanism of action of nerve growth factor.Ann Rev Biochem. 1982; 51: 845-868
- cAMP and Schwann cells promote axonal growth and functional recovery after spinal cord injury.Nat Med. 2004; 10: 610-616
- cAMP-induced repair of zebrafish spinal circuits.Science. 2004; 305: 254-258
- Taste bud adenosine -3′5′ -monophosphate phosphodiesterase: activity, subcellular distribution and kinetic parameters.Res Comm Chem Path Pharm. 1982; 38: 439-452
- The role of zinc on the trophic growth factors nerve growth factor and gustin.in: Hurley L.S. Keen C.L. Lonnerdal B. Rucker R.B. Trace elements in man and animals 6. Plenum Press, New York1988: 385-388
- Nerve growth factor (NGF) is a Ca-independent activator of Ca-dependent cAMP phosphodiesterase (PDE).Clin Res. 1985; 33: 526A
- Thyroid hormone inhibits purified taste bud membrane adenosine 3′, 5′ -monophosphate phosphodiesterase activity.Res Comm Chem Path Pharm. 1984; 43: 449-462
- Bovine taste bud cyclic adenosine 3′, 5′ monophosphate phosphodiesterase is inhibited by divalent metal ions.Res Commun Chem Pathol Pharmacol. 1983; 41: 455-472
- The Ca-activated Cl channel and its control in rat olfactory receptor neurons.J Gen Physiol. 2003; 122: 349-363
- Activation of olfactory-type cyclic nucleotide-gated channels is highly cooperative.J Physiol. 2005; 569: 91-102
- Cyclic nucleotide-gated ion channels.Physiol Rev. 2002; 82: 769-824
- In vivo assessment of local phosphodiesterase activity using tailored cyclic nucleotide-gated channels as cAMP sensors.J Gen Physiol. 2001; 118: 63-78
- cAMP is present in human nasal mucus and may act as a growth factor in cells of the olfactory epithelium.FASEB J. 2002; 16: A1153
- cAMP and cGMP are both present in human nasal mucus and play roles in control of olfactory function.FASEB J. 1994; 18: A1198
- Idiopathic hypogeusia with dysgeusia, hyposmia and dysosmia: a new syndrome.J Am Med Assoc. 1971; 217: 434-440
- Dichotomous changes in cAMP and cGMP in human parotid saliva after oral theophylline.FASEB J. 2003; 17: A1028
- Effective treatment of smell loss with theophylline.FASEB J. 2008; 22: B17-976.2
- Increased brain activation in response to odors in patients with hyposmia after theophylline treatment demonstrated by fMRI.J Comput Assist Tomogr. 1998; 22: 760-770
- On the antiapoptotic mechanism of action of theophylline in restoring smell function in patients with hyposmia.J Invest Med. 2005; 53: S402
- Deficient dietary intake of vitamin E in patients with taste and smell dysfunction: is vitamin E a cofactor in taste bud and olfactory epithelium apoptosis and in stem cell maturation and development?.Nutrition. 2003; 19: 1013-1021
- Additional evidence for the cyclic GMP signaling pathway resulting in the photophobic behavior of Stentor coeruleus.Photochem Photobiol. 2001; 74: 829-836
- Cyclic GMP metabolism and involvement in biological regulation.Annu Rev Biochem. 1979; 46: 823-896
- Structure and properties of ion channels activated by cGMP in photoreception cells of vertebrates.Kosmos. 1998; 47: 43-52
- Molecular aspects of cyclic GMP signaling.Zool Sci. 1995; 12: 131-163
- Cyclic nucleotide phosphodiesterase: pharmacology, biochemistry and function.Pharmcol Ther. 1991; 51: 13-33
- Regulation of sensory neuron precursor proliferation by cyclic GMP–dependent protein kinase.J Neurochem. 1998; 71: 1846-1853
- Sensory transduction: entering the mainstream of membrane signaling.Cell. 1991; 67: 845-851
- A cGMP-signaling pathway in a subset of olfactory sensory neurons.Proc Natl Acad Sci USA. 2000; 97: 10595-10600
- Expression of cGMP-specific phosphodiesterase 9A mRNA in the rat brain.J Neurosci. 2001; 21: 9068-9076
- Modulation by cGMP of the voltage-gated currents in newt olfactory receptor cells.Neurosci Res. 2001; 39: 327-337
- Nasal seroproteins: a new frontier in the exploration of physiology and pathology of nasal and sinus disease.in: Veldman J.E. Passali D. Lim D.J. New frontiers in immunobiology in otolaryngology. Kugler, The Hague2000: 127-152
- Report on a survey on smell in the US.Olfactory Rev. 1987; 1: 1-8
- Clinical studies in olfaction.Chem Senses. 2005; 30: i207-i209
- An open label controlled trial of theophylline for treatment of patients with hyposmia.Am J Med Sci. 2009; 337: 396-406
- A system for phenotyping hyperlipoproteinemia.Circulation. 1965; 31: 321-327
- Familial hyperlipoproteinemia.in: 2nd ed. The metabolic basis of inherited disease. McGraw Hill, New York1966: 429-468
Article info
Publication history
Published online: July 24, 2009
Accepted:
May 29,
2009
Received:
May 31,
2008
Identification
Copyright
© 2009 Elsevier Inc. Published by Elsevier Inc. All rights reserved.
