ELECTROPHYSIOLOGICAL ANALYSIS OF CHOLECYSTOKININ ACTIONS IN MAMMALIAN INFERIOR MESENTERIC GANGLION (AUTONOMIC REFLEX).

Persistent Link:
http://hdl.handle.net/10150/183872
Title:
ELECTROPHYSIOLOGICAL ANALYSIS OF CHOLECYSTOKININ ACTIONS IN MAMMALIAN INFERIOR MESENTERIC GANGLION (AUTONOMIC REFLEX).
Author:
SCHUMANN, MUHAMMAD AHMAD.
Issue Date:
1986
Publisher:
The University of Arizona.
Rights:
Copyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.
Abstract:
Cholecystokinin (CCK)-like immunoreactive materials have been localized in neurons with cell bodies in the colon and axons in the IMG of the guinea pig. The physiological significance of neuronal CCK in sympathetic prevertebral ganglia is unknown. The goal of the present studies is to test the hypothesis the CCK is a neurotransmitter in the IMG of guinea pig and rabbit. In vitro IMG preparations with or without a segment of the colon attached were utilized to conduct intracellular recordings of potentials elicited in the neurons by pressure-ejected CCK₈. The peptide triggered a depolarization with rapid onset (1-5 s) and a rate of rise (1.6 ± 0.4 mV/s) in 95% of the neurons tested. Values of the ED₅₀ for effecting depolarization average 1.1 ± 0.5 pmoles. In 59% of the cells, the depolarization was associated with a decrease in R(in) and in 20% with an increase. The remaining cells showed no change in R(in). G(Na) and G(K) were increased and decreased, respectively; potential-dependence characteristics revealed a null potential of 36 ± 9 mV in those cells exhibiting a decrease in R(in). Gastrin, caerulein, and CCK₂₇₋₃₃ effected similar depolarization. CCK₈-evoked depolarization imitated the depolarization produced either by colon distension or by nerve stimulation. Upon repeated administration of CCK₈, the response of the cells to the peptide underwent tachyphylaxis. In addition, CCK₈ desensitized the depolarization evoked by stimulation in 50% of the cells. Furthermore, in an equal percentage of neurons, CCK₈ depressed responses of the colon distension-induced depolarization. The CCK₈ has both pre- and postsynaptic sites of action is supported by lowering Ca²⁺ and administering TTX (3 μM), which caused no effect and depressed 30% of CCK-induced depolarization respectively. Spantide (SP antagonist) blocked the response to SP, but not to CCK₈, in 5 out of 6 neurons, indicating separate receptor sites for SP and CCK₈. Moveover, completely desensitizing the cell response to SP or VIP did not cross desensitize its response to CCK₈ as observed in 6 neurons. In the rabbit IMG, the physiological significance of CCK₈ excitation is unknown, since colon distension did not elicit any depolarization. These results support the hypothesis that CCK₈ or a related peptide is a neurotransmitter mediating reflex activity between the colon and the IMG in guinea pig.
Type:
text; Dissertation-Reproduction (electronic)
Keywords:
Cholecystokinin -- Analysis.; Autonomic nervous system.; Autonomic ganglia.
Degree Name:
Ph.D.
Degree Level:
doctoral
Degree Program:
Pharmacology; Graduate College
Degree Grantor:
University of Arizona
Advisor:
Kreulen, David
Committee Chair:
Burks, Thomas

Full metadata record

DC FieldValue Language
dc.language.isoenen_US
dc.titleELECTROPHYSIOLOGICAL ANALYSIS OF CHOLECYSTOKININ ACTIONS IN MAMMALIAN INFERIOR MESENTERIC GANGLION (AUTONOMIC REFLEX).en_US
dc.creatorSCHUMANN, MUHAMMAD AHMAD.en_US
dc.contributor.authorSCHUMANN, MUHAMMAD AHMAD.en_US
dc.date.issued1986en_US
dc.publisherThe University of Arizona.en_US
dc.rightsCopyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.en_US
dc.description.abstractCholecystokinin (CCK)-like immunoreactive materials have been localized in neurons with cell bodies in the colon and axons in the IMG of the guinea pig. The physiological significance of neuronal CCK in sympathetic prevertebral ganglia is unknown. The goal of the present studies is to test the hypothesis the CCK is a neurotransmitter in the IMG of guinea pig and rabbit. In vitro IMG preparations with or without a segment of the colon attached were utilized to conduct intracellular recordings of potentials elicited in the neurons by pressure-ejected CCK₈. The peptide triggered a depolarization with rapid onset (1-5 s) and a rate of rise (1.6 ± 0.4 mV/s) in 95% of the neurons tested. Values of the ED₅₀ for effecting depolarization average 1.1 ± 0.5 pmoles. In 59% of the cells, the depolarization was associated with a decrease in R(in) and in 20% with an increase. The remaining cells showed no change in R(in). G(Na) and G(K) were increased and decreased, respectively; potential-dependence characteristics revealed a null potential of 36 ± 9 mV in those cells exhibiting a decrease in R(in). Gastrin, caerulein, and CCK₂₇₋₃₃ effected similar depolarization. CCK₈-evoked depolarization imitated the depolarization produced either by colon distension or by nerve stimulation. Upon repeated administration of CCK₈, the response of the cells to the peptide underwent tachyphylaxis. In addition, CCK₈ desensitized the depolarization evoked by stimulation in 50% of the cells. Furthermore, in an equal percentage of neurons, CCK₈ depressed responses of the colon distension-induced depolarization. The CCK₈ has both pre- and postsynaptic sites of action is supported by lowering Ca²⁺ and administering TTX (3 μM), which caused no effect and depressed 30% of CCK-induced depolarization respectively. Spantide (SP antagonist) blocked the response to SP, but not to CCK₈, in 5 out of 6 neurons, indicating separate receptor sites for SP and CCK₈. Moveover, completely desensitizing the cell response to SP or VIP did not cross desensitize its response to CCK₈ as observed in 6 neurons. In the rabbit IMG, the physiological significance of CCK₈ excitation is unknown, since colon distension did not elicit any depolarization. These results support the hypothesis that CCK₈ or a related peptide is a neurotransmitter mediating reflex activity between the colon and the IMG in guinea pig.en_US
dc.typetexten_US
dc.typeDissertation-Reproduction (electronic)en_US
dc.subjectCholecystokinin -- Analysis.en_US
dc.subjectAutonomic nervous system.en_US
dc.subjectAutonomic ganglia.en_US
thesis.degree.namePh.D.en_US
thesis.degree.leveldoctoralen_US
thesis.degree.disciplinePharmacologyen_US
thesis.degree.disciplineGraduate Collegeen_US
thesis.degree.grantorUniversity of Arizonaen_US
dc.contributor.advisorKreulen, Daviden_US
dc.contributor.chairBurks, Thomasen_US
dc.contributor.committeememberNelson, Daviden_US
dc.contributor.committeememberLukas, Ronalden_US
dc.identifier.proquest8623861en_US
dc.identifier.oclc697809038en_US
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