Proteinase-activated receptors in the nucleus of the solitary tract: evidence for glial-neural interactions in autonomic control of the stomach.
Bleeding head injury is associated with gastric stasis, a symptom of collapse of autonomic control of the gut described by Cushing around 1932. Recent work suggests that the proteinase thrombin, produced secondary to bleeding, may be the root cause. Results from our in vivo physiological studies show that fourth ventricular injection of PAR1 agonists, as well as thrombin itself, produced significant reductions in gastric transit in the awake rat. We expected that the PAR1 effect to inhibit gastric transit was the result of direct action on vagovagal reflex circuitry in the dorsal medulla. Surprisingly, our immunohistochemical studies demonstrated that PAR1 receptors are localized exclusively to the astrocytes and not the neurons in the nucleus of the solitary tract (NST; principal locus integrating visceral afferent input and part of the gastric vagovagal reflex control circuitry). Our in vitro calcium imaging studies of hindbrain slices revealed that PAR1 activation initially causes a dramatic increase in astrocytic calcium, followed seconds later by an increase in calcium signal in NST neurons. The neuronal effect, but not the astrocytic effect, of PAR1 activation was eliminated by glutamate receptor antagonism. TTX did not eliminate the effects of PAR1 activation on either glia or neurons. Thus, we propose that glia are the primary CNS sensors for PAR agonists and that the response of these glial cells drives the activity of adjacent (e.g., NST) neurons. These results show, for the first time, that changes in autonomic control can be directly signaled by glial detection of local chemical stimuli.
Hermann
Gerlinda E
GE
Autonomic Neuroscience Laboratory, Pennington Biomedical Research Center, Louisiana State University System, Baton Rouge, Louisiana 70808, USA. gerlinda.hermann@pbrc.edu
Van Meter
Montina J
MJ
Rood
Jennifer C
JC
Rogers
Richard C
RC
D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D002118:Calcium / Q000378:metabolism*; D018691:Excitatory Amino Acid Antagonists / Q000008:administration & dosage; D005260:Female; D018698:Glutamic Acid / Q000378:metabolism; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D008297:Male; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D010446:Peptide Fragments / Q000008:administration & dosage; D051381:Rats; D044463:Receptor, PAR-1 / Q000819:agonists / Q000378:metabolism*; D012249:Rhombencephalon / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D026941:Sodium Channel Blockers / Q000008:administration & dosage; D017552:Solitary Nucleus / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D013270:Stomach / Q000502:physiology*; D013779:Tetrodotoxin / Q000008:administration & dosage; D013917:Thrombin / Q000008:administration & dosage; D013997:Time Factors
D018691:Excitatory Amino Acid Antagonists; D010446:Peptide Fragments; D044463:Receptor, PAR-1; D026941:Sodium Channel Blockers; D018698:Glutamic Acid; D013779:Tetrodotoxin; D013917:Thrombin; D002118:Calcium