PMID- 2498332
OWN - NLM
STAT- MEDLINE
DCOM- 19890705
LR  - 20210318
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 264
IP  - 16
DP  - 1989 Jun 5
TI  - Receptor density determines secretory response patterns mediate by inositol 
      lipid-derived second messengers. Comparison of thyrotropin-releasing hormone and 
      carbamylcholine actions in thyroid-stimulating hormone-secreting mouse pituitary 
      tumor cells.
PG  - 9438-43
AB  - Signal transduction by thyrotropin-releasing hormone (TRH) and carbamylcholine 
      (CCH) in some cells is mediated by inositol lipid hydrolysis forming the second 
      messengers, inositol 1,4,5-trisphosphate (I-1,4,5-P3) and 1,2-diacylglycerol, and 
      causing elevation of cytoplasmic free Ca2+ concentration [( Ca2+]i). In mouse 
      thyrotropic tumor (TtT) cells, maximally effective doses of TRH caused biphasic 
      stimulation of thyroid-stimulating hormone (TSH) secretion, whereas CCH 
      stimulated monophasic sustained TSH secretion without a burst phase. TRH, at 
      maximally effective doses, stimulated a rapid marked increase in I-1,4,5-P3 which 
      was associated with a rapid elevation of [Ca2+]i to approximately 1000 nM, 
      whereas maximally effective doses of CCH caused little increase in I-1,4,5-P3 and 
      no burst elevation of [Ca2+]i. Both TRH and CCH caused sustained modest (to 
      210-280 nM) elevations of [Ca2+]i which were inhibited by voltage-sensitive 
      channel-blocking agents and stimulated sustained hydrolysis of inositol lipids. 
      CCH-like responses were observed when TtT cells were stimulated by low doses of 
      TRH. In TtT cells prepared from five tumors, the ratio of the number of TRH 
      receptors to muscarinic receptors ranged from 10 to 40:1. Lastly, CCH-like 
      responses were observed with maximally effective doses of TRH when the TRH 
      receptor number was down-regulated to a level similar to that of muscarinic 
      receptors. These data suggest that the kinetic pattern of stimulated TSH 
      secretion caused by secretagogues that use the inositol lipid signal transduction 
      pathway is determined by the density of receptors. In particular, there appears 
      to be a minimal number of receptor-ligand complexes which is required to generate 
      rapidly sufficient I-1,4,5-P3 to release intracellular Ca2+ and cause a secretory 
      burst.
FAU - Winicov, I
AU  - Winicov I
AD  - Department of Medicine, Cornell University Medical College, New York.
FAU - Gershengorn, M C
AU  - Gershengorn MC
LA  - eng
GR  - DK33468/DK/NIDDK NIH HHS/United States
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Inositol Phosphates)
RN  - 0 (Receptors, Muscarinic)
RN  - 0 (Sugar Phosphates)
RN  - 5Y5F15120W (Thyrotropin-Releasing Hormone)
RN  - 85166-31-0 (Inositol 1,4,5-Trisphosphate)
RN  - 8Y164V895Y (Carbachol)
RN  - 9002-71-5 (Thyrotropin)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Animals
MH  - Calcium/physiology
MH  - Carbachol/*pharmacology
MH  - Inositol 1,4,5-Trisphosphate
MH  - Inositol Phosphates/biosynthesis/*metabolism/physiology
MH  - Kinetics
MH  - Mice
MH  - Pituitary Neoplasms/*metabolism
MH  - Receptors, Muscarinic/drug effects/*physiology
MH  - Second Messenger Systems/*drug effects
MH  - Sugar Phosphates/*metabolism
MH  - Thyrotropin/*metabolism
MH  - Thyrotropin-Releasing Hormone/*pharmacology
MH  - Tumor Cells, Cultured
EDAT- 1989/06/05 00:00
MHDA- 1989/06/05 00:01
CRDT- 1989/06/05 00:00
PHST- 1989/06/05 00:00 [pubmed]
PHST- 1989/06/05 00:01 [medline]
PHST- 1989/06/05 00:00 [entrez]
AID - S0021-9258(18)60551-4 [pii]
PST - ppublish
SO  - J Biol Chem. 1989 Jun 5;264(16):9438-43.