Article date: May 2003
By: Mitsuhiko Saita, Anthony J M Verberne in Volume 139, Issue 2, pages 415-423
The role of peripheral 5‐hydroxytryptamine (5‐HT3) receptors and cholecystokinin type 1 (CCK1) 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 α‐chloralose‐anaesthetized rats.
CCK (1 and 4 μg kg−1, i.v.) and PBG (2 and 10 μg 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.
Devazepide (0.5 mg kg−1, i.v.), a selective CCK1 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‐HT3 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.
These experiments suggest that systemically administered CCK acts directly through CCK1 receptors to modulate sympathetic vasomotor function. In addition, the actions of CCK also are partly dependent on activation of 5‐HT3 receptors. CCK may release 5‐HT which then acts at 5‐HT3 receptors to produce sympathetic vasomotor inhibition. In contrast, the actions of PBG are entirely dependent on 5‐HT3 receptors and are independent of any actions at the CCK1 receptor.
The role of peripheral 5‐hydroxytryptamine (5‐HT3) receptors and cholecystokinin type 1 (CCK1) 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 α‐chloralose‐anaesthetized rats.
CCK (1 and 4 μg kg−1, i.v.) and PBG (2 and 10 μg 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.
Devazepide (0.5 mg kg−1, i.v.), a selective CCK1 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‐HT3 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.
These experiments suggest that systemically administered CCK acts directly through CCK1 receptors to modulate sympathetic vasomotor function. In addition, the actions of CCK also are partly dependent on activation of 5‐HT3 receptors. CCK may release 5‐HT which then acts at 5‐HT3 receptors to produce sympathetic vasomotor inhibition. In contrast, the actions of PBG are entirely dependent on 5‐HT3 receptors and are independent of any actions at the CCK1 receptor.
British Journal of Pharmacology (2003) 139, 415–423. doi:10.1038/sj.bjp.0705245
DOI: 10.1038/sj.bjp.0705245
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