Roles for CCK1 and 5-HT3 receptors in the effects of CCK on presympathetic vasomotor neuronal discharge in the rat.
1 The role of peripheral 5-hydroxytryptamine (5-HT(3)) receptors and cholecystokinin type 1 (CCK(1)) receptors in the inhibitory effects of phenylbiguanide (PBG) and CCK on arterial blood pressure, heart rate and the discharge of presympathetic vasomotor neurones of the rostral ventrolateral medulla (RVLM) was studied in alpha-chloralose-anaesthetized rats. 2 CCK (1 and 4 micro g kg(-1), i.v.) and PBG (2 and 10 micro g kg(-1), i.v.) reduced arterial blood pressure and heart rate, and inhibited the discharge of single RVLM presympathetic vasomotor neurones in a dose-related manner. 3 Devazepide (0.5 mg kg(-1), i.v.), a selective CCK(1) receptor antagonist, blocked the effects of CCK on arterial blood pressure, heart rate and neuronal discharge but did not significantly alter these responses to PBG. MDL72222 (0.1 mg kg(-1), i.v.), a selective 5-HT(3) receptor antagonist, blocked the effects of PBG on arterial blood pressure, heart rate and presympathetic neuronal discharge. MDL72222 attenuated the effects of CCK on arterial blood pressure, heart rate and RVLM presympathetic neuronal discharge. Vehicle did not significantly alter any of the responses to CCK or PBG. 4 These experiments suggest that systemically administered CCK acts directly through CCK(1) receptors to modulate sympathetic vasomotor function. In addition, the actions of CCK also are partly dependent on activation of 5-HT(3) receptors. CCK may release 5-HT which then acts at 5-HT(3) receptors to produce sympathetic vasomotor inhibition. In contrast, the actions of PBG are entirely dependent on 5-HT(3) receptors and are independent of any actions at the CCK(1) receptor.
Saita
Mitsuhiko
M
Department of Medicine, Clinical Pharmacology and Therapeutics Unit, Austin and Repatriation Medical Centre, University of Melbourne, Heidelberg, Victoria 3084, Australia. antonius@unimelb.edu.au
Verberne
Anthony J M
AJ
D000818:Animals; D001645:Biguanides / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D002766:Cholecystokinin / Q000494:pharmacology / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D008297:Male; D008526:Medulla Oblongata / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D043886:Receptor, Cholecystokinin A / Q000819:agonists / Q000037:antagonists & inhibitors / Q000502:physiology*; D044406:Receptors, Serotonin, 5-HT3 / Q000502:physiology*; D058827:Serotonin 5-HT3 Receptor Agonists; D058831:Serotonin 5-HT3 Receptor Antagonists; D014326:Tropanes / Q000494:pharmacology; D014666:Vasomotor System / Q000187:drug effects / Q000502:physiology*
D001645:Biguanides; D043886:Receptor, Cholecystokinin A; D044406:Receptors, Serotonin, 5-HT3; D058827:Serotonin 5-HT3 Receptor Agonists; D058831:Serotonin 5-HT3 Receptor Antagonists; D014326:Tropanes; D002766:Cholecystokinin; C042253:bemesetron; C008846:phenyl biguanide