TY - JOUR
T1 - Electrophysiological and autoradiographical evidence for cholecystokinin A receptors on rat isolated nodose ganglia
AU - Widdop, Robert E.
AU - Krstew, Elena
AU - Mercer, Linda D.
AU - Carlsberg, Mats
AU - Beart, Philip M.
AU - Jarrott, Bevyn
PY - 1994/1/1
Y1 - 1994/1/1
N2 - The sulphated octapeptide, cholecystokinin (CCK-8S), is believed to be a neurotransmitter of vagal sensory neurones, and here the presence of functional receptors for CCK-8S in the rat vagus nerve has been investigated by electrophysiological and autoradiographic techniques. CCK-8S caused concentration-dependent depolarizations when superfused over the rat isolated nodose ganglion at 37°C as measured by a silicone grease gap technique. Concentration-response curves to CCK-8S were shifted to the right by low concentrations of the CCKA receptor antagonist, Devazepide, but not by the CCKB receptor antagonist, L-365,260, data which indicate that receptors were of the CCKA subtype. Consistent with this notion, the CCKB agonist, unsulphated CCK-8, was without effect until high concentrations (> 1 μM) were used. A synthetic analogue of CCK-8S, d-Tyr25(Nle28,31)-CCK 25-33S, which has been reported to be more stable and peptidase-resistant than CCK-8S, was equipotent with CCK-8S in depolarizing the nodose ganglion. When d-Tyr25(Nle28,31)-CCK 25-33S was labelled with 125I, it bound to tissue sections of nodose ganglion. By light microscopic autoradiography, silver grains were found to be highly localized over cell bodies of vagal sensory neurones. An excess of CCK-8S inhibited binding as did Devazepide, but not L-365,260, confirming that binding sites were CCKA subtype receptors. These results indicate the existence of functional CCKA receptors in the nodose ganglion and strengthen the case for the involvement of vagal sensory neurones in gastric emptying and satiety.
AB - The sulphated octapeptide, cholecystokinin (CCK-8S), is believed to be a neurotransmitter of vagal sensory neurones, and here the presence of functional receptors for CCK-8S in the rat vagus nerve has been investigated by electrophysiological and autoradiographic techniques. CCK-8S caused concentration-dependent depolarizations when superfused over the rat isolated nodose ganglion at 37°C as measured by a silicone grease gap technique. Concentration-response curves to CCK-8S were shifted to the right by low concentrations of the CCKA receptor antagonist, Devazepide, but not by the CCKB receptor antagonist, L-365,260, data which indicate that receptors were of the CCKA subtype. Consistent with this notion, the CCKB agonist, unsulphated CCK-8, was without effect until high concentrations (> 1 μM) were used. A synthetic analogue of CCK-8S, d-Tyr25(Nle28,31)-CCK 25-33S, which has been reported to be more stable and peptidase-resistant than CCK-8S, was equipotent with CCK-8S in depolarizing the nodose ganglion. When d-Tyr25(Nle28,31)-CCK 25-33S was labelled with 125I, it bound to tissue sections of nodose ganglion. By light microscopic autoradiography, silver grains were found to be highly localized over cell bodies of vagal sensory neurones. An excess of CCK-8S inhibited binding as did Devazepide, but not L-365,260, confirming that binding sites were CCKA subtype receptors. These results indicate the existence of functional CCKA receptors in the nodose ganglion and strengthen the case for the involvement of vagal sensory neurones in gastric emptying and satiety.
KW - Autoradiography
KW - Cholecystokinin
KW - Cholecystokinin receptor subtypes
KW - Devazepide
KW - Electrophysiology
KW - Nodose Ganglion
UR - http://www.scopus.com/inward/record.url?scp=0027979096&partnerID=8YFLogxK
U2 - 10.1016/0165-1838(94)90145-7
DO - 10.1016/0165-1838(94)90145-7
M3 - Article
C2 - 8120343
AN - SCOPUS:0027979096
SN - 0165-1838
VL - 46
SP - 65
EP - 73
JO - Journal of the Autonomic Nervous System
JF - Journal of the Autonomic Nervous System
IS - 1-2
ER -