Possible role of cholecystokinin-A receptors in regulation of thyrotropin (TSH) secretion in male rats.
We studied the importance of cholecystokinin (CCK) system in the regulation of thyrotropin (TSH) and prolactin (PRL) secretion in male rats. To this end, we tested the effects of both unselective CCK agonists CCK-8 and caerulein, and CCK-B selective agonists CCK-4 and pentagastrin as well as the selective CCK antagonists (devazepide and L-365,260) at wide dose-ranges on the cold-stimulated and TRH-induced TSH and PRL secretion. Caerulein, given s.c. 15 min before sacrifice, decreased TSH levels at 5 micrograms/kg. In time course-studies, the maximum inhibition was seen at 15 min but the effect lasted at least 30, but less than 60 min. Also CCK-8 decreased TSH levels at the doses of 20 and 50 micrograms/kg at 15 min. Devazepide and L-365,260 did not affect TSH or PRL levels at any dose. The effect of caerulein (5 micrograms/kg) was antagonized by devazepide, a CCK-A antagonist, at 100 micrograms/kg, but not by a CCK-B antagonist L-365,260 tested at a wide dose range. PRL levels were not affected by any treatment. Caerulein (5 micrograms/kg), given at the same time as TRH (500 ng/kg), inhibited the TRH-induced TSH levels at 15 min, but not at 30 or 60 min. CCK-8 (50 micrograms/kg), CCK-4 (100 micrograms/kg) and pentagastrin (500 micrograms/kg) did not affect the TRH-induced TSH secretion. The results probably indicate that CCK-A receptor stimulation inhibits TSH secretion at the level of the anterior pituitary gland. PRL levels in male rats are not affected by CCK system.
Männistö
P T
PT
Department of Pharmacology and Toxicology, University of Helsinki, Finland.
Peuranen
E
E
Harro
J
J
Vasar
E
E
D000818:Animals; D001570:Benzodiazepinones / Q000494:pharmacology; D002108:Ceruletide / Q000494:pharmacology; D002766:Cholecystokinin / Q000037:antagonists & inhibitors; D003080:Cold Temperature; D020109:Devazepide; D004305:Dose-Response Relationship, Drug; D008297:Male; D010418:Pentagastrin / Q000494:pharmacology; D010671:Phenylurea Compounds; D011388:Prolactin / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D011949:Receptors, Cholecystokinin / Q000037:antagonists & inhibitors / Q000502:physiology*; D012844:Sincalide / Q000494:pharmacology; D013758:Tetragastrin / Q000494:pharmacology; D013972:Thyrotropin / Q000378:metabolism*
D001570:Benzodiazepinones; D010671:Phenylurea Compounds; D011949:Receptors, Cholecystokinin; D013758:Tetragastrin; C058121:L 365260; D002108:Ceruletide; D011388:Prolactin; D013972:Thyrotropin; D002766:Cholecystokinin; D010418:Pentagastrin; D020109:Devazepide; D012844:Sincalide