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Title: Activation of cholecystokinin (CCK 1) and serotonin (5-HT 3) receptors increases the discharge of pancreatic vagal afferents.
Austin Authors: Mussa, Bashair M;Sartor, Daniela M;Verberne, Anthony J M 
Affiliation: University of Melbourne, Department of Medicine, Clinical Pharmacology and Therapeutics Unit, Austin Health, Heidelberg 3084, Victoria, Australia
Issue Date: 9-Nov-2008
Publication information: European Journal of Pharmacology 2008; 601(1-3): 198-206
Abstract: Cholecystokinin and serotonin are released from the gastrointestinal tract in response to the products of digestion and play critical roles in mediating pancreatic secretion via vago-vagal reflex pathways. This study was designed to investigate the effects of activation of cholecystokinin CCK(1) and serotonin (5-hydroxytryptamine, 5-HT) 5-HT(3) receptors on pancreatic vagal afferent discharge and to determine whether there is an interaction between these receptors. Male Sprague Dawley rats anaesthetised with isoflurane (1.5%/100% O(2)) were used in all experiments. The effects of systemic administration of cholecystokinin and the serotonin 5-HT(3) receptor agonist phenylbiguanide on pancreatic vagal afferent discharge were recorded before and after administration of cholecystokinin CCK(1) and serotonin 5-HT(3) receptor antagonists. Cholecystokinin (0.1-10 microg/kg, i.v.) and phenylbiguanide (1 and 10 microg/kg, i.v.) increased pancreatic vagal afferent discharge dose-dependently. Cholecystokinin CCK(1) receptor antagonists, lorglumide (10 mg/kg, i.v.) and devazepide (0.5 mg/kg, i.v.), reduced cholecystokinin- and phenylbiguanide-induced increases in pancreatic vagal afferent discharge significantly (n=5, P<0.05). On the other hand, serotonin 5-HT(3) receptor blockade with granisetron (1 mg/kg, i.v.) or MDL72222 ([(1S,5R)-8-methyl-8-azabicyclo[3.2.1]octan-3-yl] 3,5-dichlorobenzoate; 0.1 mg/kg, i.v.) inhibited the pancreatic vagal afferent discharge responses to phenylbiguanide but not those to cholecystokinin. This study has confirmed that cholecystokinin and phenylbiguanide activate pancreatic vagal afferent discharge via activation of cholecystokinin CCK(1) and serotonin 5-HT(3) receptors, respectively. In addition, it has demonstrated that (i) the serotonin 5-HT(3) agonist phenylbiguanide acts partly via an interaction with cholecystokinin CCK(1) receptors, and (ii) the actions of cholecystokinin are not dependent on serotonin 5-HT(3) receptor activation.
Gov't Doc #: 19026634
DOI: 10.1016/j.ejphar.2008.11.007
Type: Journal Article
Subjects: Animals
Biguanides.administration & dosage.pharmacology
Cholecystokinin.administration & dosage.metabolism
Dose-Response Relationship, Drug
Neurons, Afferent.metabolism
Rats, Sprague-Dawley
Receptor, Cholecystokinin A.drug effects.metabolism
Receptors, Serotonin, 5-HT3.drug effects.metabolism
Serotonin Receptor Agonists.administration & dosage.pharmacology
Vagus Nerve.metabolism
Appears in Collections:Journal articles

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