期刊
JOURNAL OF NEUROPHYSIOLOGY
卷 94, 期 4, 页码 2763-2771出版社
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/jn.00351.2005
关键词
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资金
- NIDDK NIH HHS [DK-56373, DK-55530, R01 DK055530-08, R01 DK056373, R01 DK055530] Funding Source: Medline
Cholecystokinin (CCK) is released from enteroendocrine cells after ingestion of nutrients and induces multiple effects along the gastrointestinal tract, including gastric relaxation and short-term satiety. We used whole cell patch-clamp and immunohistochemical techniques in rat brain stem slices to characterize the effects of CCK. In 45% of the neurons of nucleus tractus solitarius subnucleus centralis (cNTS), perfusion with the sulfated form of CCK (CCK-8s) increased the frequency of spontaneous excitatory currents (sEPSCs) in a concentration-dependent manner ( 1 - 300 nM). The threshold for the CCK-8s excitatory effect was 1 nM, the EC50 was 20 nM, and E-max was 100 nM. The excitatory effects of CCK-8s were still present when the slices were preincubated with tetrodotoxin or bicuculline or when the recordings were conducted with Cs+ electrodes. Pretreatment with the CCK-A receptor antagonist, lorglumide (1 mu M), antagonized the effects of CCK-8s, whereas perfusion with the CCK-B preferring agonist CCK-8 nonsulfated (CCK-ns, 1 mu M) did not affect the frequency of sEPSCs. Similarly, pretreatment with the CCK-B receptor antagonist, triglumide (1 mu M), did not prevent the actions of CCK-8s. Although the majority (i.e., 76%) of CCK-8s unresponsive cNTS neurons had a bipolar somata shape and were TH-IR negative, no differences were found in either the morphological or the neurochemical phenotype of cNTS neurons responsive to CCK-8s. Our results suggest that the excitatory effects of CCK-8s on terminals impinging on a subpopulation of cNTS neurons are mediated by CCK-A receptors; these responsive neurons, however, do not have morphological or neurochemical characteristics that automatically distinguish them from nonresponsive neurons.
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