Systemic Cholecystokinin Differentially Affects Baro-activated GABAergic

Susan C. Mobley, Daniel A. Mandel, and Ann M. Schreihofer
Department of Physiology, Medical College of Georgia, Augusta, Georgia

J Neurophysiol

First published August 16, 2006; doi:10.1152/jn.00526.2006


  In this article, the actions of Cholecystokinin (CCK) on CVLM and SNA were investigated. CCK will cause a decrease in splanchnic nerve activity (sSNA). CCK is released after the ingestion of a meal. First they looked how CCK will affect sSNA and arterial pressure (AP). They recorded the neurons activity in the CVLM during all procedures. what they found was that in the majority of animals depressor responses within the first 15 seconds. They also found that the response was not a smooth but that it decrease some at first and then came back up and was followed by a greater depressor response in AP and also in sSNA (see fig 1A). In a few animals there was no AP depressor response however, there was a decrease in the sSNA. Then the neurons were labeled with biotinamide and the GABAergic phenotype was confirmed.Next they investigated how CCK would infleunce the activity of baro-inhibited neurons. By using aortic snare AP was raised and those neurons that had decrease in activity were considered baro-inhibited CVLM neurons. Then CCK was injected and the activity of these neuron was decreased and several neurons were silenced. In order to determine if CVLM was essential to the effects of CCK, CVLM was inhibited and CCK was injected. Before the muscimol (mus), a GABA A receptor agonist, they gave phenylbiguanide (PBG) to show the maximal activity of CVLM, next CCK was given they saw a decrease in sSNA, AP and HR. Then they gave mus bilaterally and then injected CCK what they saw was an increase in SNA and a decrease in HR. As for the PBG after mus it was reversed also instead they saw increase in all responses. Because inhibiting the CVLM causes an increase in SNA it could be possible that CCK could be potentiating the affects of Acetylocholine at the nicotinic receptor. So they gave hydralazine a vasodilator to cause an increase in sSNA and then gave CCK which inhibited the sSNA. Therefore the increase seen in the muscimol protocol was not due to the elevation of SNA.

 The interesting thing is that PBG maximally activates CVLM neurons but CCK only activates about 30% of the CVLM neuron population suggesting that certain neurons are resposible for the control of specific neurons in RVLM that control specific nerves. for instance injecting CCK causes increase in lumbar SNA. CCK also has cardiovascular responses it mediate, it can cause vasodilation at the blood vessels. It can also cause bradycardia by acting at CCK A receptors on the heart, this is most likely why after inhibiting the CVLM bilaterally, there was still a decrease in HR. CCK therefore does not depend on the CVLM pathway to control HR. PBG however does which is why after the muscimol there was increases in HR, AP and sSNA.