CCKA receptors mediate slow depolarizations in cultured mammalian sympathetic neurons.
The effect of cholecystokinin octapeptide (CCK-8) was examined in guinea-pig celiac ganglion (CG) neurons in primary culture using standard intracellular recording techniques. Sulfated CCK-8 (CCK-8S; 1 microM) evoked slow depolarizing responses in 94% of CG neurons tested. In contrast, membrane potential was not affected by nonsulfated CCK-8 (CCK-8NS; 1 microM), CCK tetrapeptide (CCK-4; 1 microM), or gastrin (1 microM). The selective CCKA receptor antagonist L 364,718 potently inhibited CCK-8S-induced slow depolarizations (IC50 2.9 pM). In contrast, the selective CCKB receptor antagonist L 365,260 was a weak inhibitor of CCK-8S-induced slow depolarizations (IC50 1.3 microM). The depolarizing responses to CCK-8S were associated with an average increase in cell input resistance of 61%. Single electrode voltage clamp experiments indicated that CCK-8S-induced depolarizations were associated with a slow inward shift in holding current. Thus, the present findings indicate that guinea-pig cultured CG neurons are endowed with excitatory CCKA receptors the activation of which elicits a decrease in membrane conductance, thereby resulting in slow depolarizations.
Knoper
S R
SR
Department of Pharmacology, College of Medicine, University of Arizona, Tucson 85724.
Meehan
A G
AG
Purnyn
S
S
Coggan
J S
JS
Anthony
T L
TL
Kreulen
D L
DL
D000818:Animals; D001570:Benzodiazepinones / Q000494:pharmacology; D002478:Cells, Cultured; D020109:Devazepide; D005260:Female; D005728:Ganglia, Sympathetic / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D005755:Gastrins / Q000494:pharmacology; D006168:Guinea Pigs; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D010671:Phenylurea Compounds; D011949:Receptors, Cholecystokinin / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000502:physiology*; D012844:Sincalide / Q000494:pharmacology; D013758:Tetragastrin / Q000494:pharmacology
D001570:Benzodiazepinones; D005755:Gastrins; D010671:Phenylurea Compounds; D011949:Receptors, Cholecystokinin; D013758:Tetragastrin; C058121:L 365260; D020109:Devazepide; D012844:Sincalide