Sulfated cholecystokinin octapeptide in the rat: pontomedullary distribution and modulation of the respiratory pattern.
We performed anatomical and physiological studies to determine the site and actions of sulfated cholecystokinin octapeptide (CCK8-S) on breathing. Peptide locations were determined by combined immunodetection of CCK8-S- containing synaptic varicosities and retrograde labeling of medullary neurons projecting to the ventral respiratory group. Retrogradely labeled neurons and CCK8-S immunolabeled varicosities overlapped within the nuclei of the solitary tract, ventral respiratory group, and the Kolliker-Fuse nucleus. Additional CCK8-S immunoreactive terminals were located in the rostroventrolateral medullary reticular nucleus, lateral paragigantocellular reticular nucleus, and the caudal pontine reticular nucleus. The respiratory effects of CCK8-S, which binds to CCK(A) and CCK(B) receptors, were examined by intravenous injection in adult rats and by bath application in the in vitro neonatal rat brainstem - spinal cord preparation. CCK8-S produced an increase in the mean amplitude of diaphragmatic electromyogram (EMG) of 28 +/- 35% (SD) and a decrease in mean respiratory interval of 13 +/- 4% in vivo. In vitro, CCK8-S significantly increased inspiratory duration and decreased respiratory interval, primarily by shortening expiratory duration. CCK8-unsulfated, a specific agonist for CCK(B) receptors, did not produce these effects. CCK8-S effects in the in vitro preparation were partially blocked by the CCK receptor antagonist lorglumide (final bath concentration 600 nM). These results suggest that CCK8-S modulates the respiratory rhythm via CCK(A) receptors within one or more medullary or pontine respiratory groups in both neonatal and adult rats.
Ellenberger
H H
HH
Department of Anatomy and Neurobiology, Faculty of Medicine, Dalhousie University, Halifax, NS, Canada. hellenbe@ccpm.edu
Smith
F M
FM
D000818:Animals; D004305:Dose-Response Relationship, Drug; D005260:Female; D008297:Male; D008526:Medulla Oblongata / Q000737:chemistry / Q000187:drug effects*; D011149:Pons / Q000737:chemistry / Q000187:drug effects*; D051381:Rats; D020318:Rats, Long-Evans; D017207:Rats, Sprague-Dawley; D011949:Receptors, Cholecystokinin / Q000145:classification / Q000187:drug effects / Q000502:physiology; D012119:Respiration / Q000187:drug effects*; D012844:Sincalide / Q000032:analysis / Q000494:pharmacology*; D013431:Sulfates / Q000494:pharmacology
D011949:Receptors, Cholecystokinin; D013431:Sulfates; D012844:Sincalide