CCK receptor subtype in insulin-producing cells: a combined functional and in situ hybridization study in rat islets and a rat insulinoma cell line.
Cholecystokinin (CCK) stimulates insulin secretion. It is, however, not established whether CCK receptors are expressed in insulin-producing cells. We therefore investigated, by in situ hybridization, whether CCK-A or CCK-B receptor mRNA could be detected in normal rat pancreatic islets and in the rat insulinoma cell line, RINm5F. The CCK-A, but not the CCK-B, receptor transcript was detected in both islets and RINm5F cells. Islet CCK-A receptors were mostly confined to the center of the islets corresponding to the distribution of the B cells. In RINm5F cells, insulin release was not significantly affected by cholecystokinin (CCK)-8-S (10(-13) to 10(-7) M), which is in contrast to the insulinotropic effect of CCK-8-S in normal rat islets. Similarly, in FURA-2AM-loaded cells, CCK-8-S (10(-11) to 10(-7) M) was without effect on the intracellular Ca2+ concentration ([Ca2+]ic) in RINm5F cells, whereas CCK-8-S (10(-7) M) markedly increased [Ca2+]ic (by 366+/-2 nM (P < 0.001) in normal rat islet cells. We conclude that the CCK-A, but not the CCK-B, receptor subtype is expressed in both normal rat islets and in the rat insulinoma-derived cell line RINmS5F. There is, however, a functional difference between normal islets and the RINm5F cells with respect to effects of CCK-8-S on insulin release and [Ca2+]ic.
Karlsson
S
S
Department of Medicine, Malmö, The Wallenberg Laboratory, Malmö University Hospital, Sweden. Sven.Karlsson@medforsk.mas.lu.se
Sundler
F
F
Ahrén
B
B
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002217:Carbachol / Q000494:pharmacology; D016257:Fura-2 / Q000031:analogs & derivatives / Q000378:metabolism; D005753:Gastric Mucosa / Q000166:cytology / Q000378:metabolism; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007328:Insulin / Q000378:metabolism; D007340:Insulinoma / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000166:cytology / Q000378:metabolism; D007515:Islets of Langerhans / Q000378:metabolism*; D008297:Male; D010179:Pancreas / Q000166:cytology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011949:Receptors, Cholecystokinin / Q000145:classification / Q000378:metabolism*; D012844:Sincalide / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D007328:Insulin; D012333:RNA, Messenger; D011949:Receptors, Cholecystokinin; C049925:fura-2-am; D002217:Carbachol; D012844:Sincalide; D002118:Calcium; D016257:Fura-2