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Release of substance P by low oxygen in the rabbit carotid body: evidence for the involvement of calcium channels
- Source :
- Brain Research. 892:359-369
- Publication Year :
- 2001
- Publisher :
- Elsevier BV, 2001.
-
Abstract
- Carotid bodies from diverse species contain substance P (SP), an 11-residue peptide that belongs to the tachykinin peptide family. Previous studies indicated that SP is excitatory to the carotid body and is associated with sensory response to hypoxia. However, release of SP from the carotid body during hypoxia has not been documented. In the present study, we determined whether hypoxia releases SP from the carotid body and further characterized the mechanism(s) associated with SP release by low oxygen. The release of SP from superfused rabbit carotid body was determined by an enzyme immunoassay (EIA). SP-like immunoreactivity was localized to many glomus cells and nerve fibers and the concentration of SP in the rabbit carotid body was 1.5+/-0.1 ng/mg protein. For release studies, carotid bodies (n=56) were superfused with a modified Tyrode medium containing Hepes buffer, pH 7.4, saturated with either room air (normoxia) or hypoxic gas mixtures. The basal release of SP during normoxia was 51.0+/-1.5 fmol/min per mg protein. Hypoxia increased SP release from the carotid body and the magnitude of release is dependent on the severity of hypoxic stimulus. Moderate hypoxia (pO2, 79+/-4 mmHg) stimulated SP release by approximately 50%, whereas SP release during severe hypoxia (pO2, 11+/-6 mmHg) was 2-fold higher than the normoxic control. A similar pattern of SP release was also observed when superfusion medium containing CO2-HCO3 buffer, pH 7.4, was used for release studies. To examine the mechanism(s) associated with hypoxia-induced SP release from the carotid body, moderate level of hypoxia (12% O2+N2) was used. Omission of calcium in the superfusion medium markedly attenuated hypoxia-induced SP release (95%), whereas the basal release of SP was unaffected. Cd2+ (100 microM), a voltage-dependent Ca2+ channel blocker, abolished hypoxia-induced SP release. About 85% of SP release by hypoxia was inhibited by omega-conotoxin GVIA (1 microM), an N-type Ca2+ channel blocker, whereas nitrendipine (1.5 microM), an inhibitor of L-type Ca2+ channel partially attenuated ( approximately 65%) hypoxia-induced SP release. By contrast, omega-agatoxin TK (50 nM), a P/Q-type Ca2+ channel inhibitor, had no significant effect (P0.05, n=6). These results suggest that SP is released from the rabbit carotid body by hypoxia that depends on the severity of the hypoxic stimulus. Further, SP release by hypoxia is a calcium-dependent process and is primarily mediated by N- and L-type Ca2+ channels.
- Subjects :
- Male
medicine.medical_specialty
Calcium Channels, L-Type
chemistry.chemical_element
Substance P
Calcium
N-type calcium channel
Immunoenzyme Techniques
Calcium Channels, N-Type
Glomus cell
Internal medicine
medicine
Animals
Channel blocker
L-type calcium channel
Molecular Biology
Carotid Body
Voltage-dependent calcium channel
Chemistry
General Neuroscience
Hypoxia (medical)
Calcium Channel Blockers
Immunohistochemistry
Endocrinology
medicine.anatomical_structure
Cerebrovascular Circulation
Hypoxia-Ischemia, Brain
Carotid body
Calcium Channels
Rabbits
Neurology (clinical)
medicine.symptom
Developmental Biology
Subjects
Details
- ISSN :
- 00068993
- Volume :
- 892
- Database :
- OpenAIRE
- Journal :
- Brain Research
- Accession number :
- edsair.doi.dedup.....03ca602a7ab7a9742bcb46b0302c2baa