PMID- 2547206 OWN - NLM STAT- MEDLINE DCOM- 19890901 LR - 20190818 IS - 0196-9781 (Print) IS - 0196-9781 (Linking) VI - 10 IP - 2 DP - 1989 Mar-Apr TI - Functional corticotropin-releasing factor (CRF) receptors in mouse spleen: evidence from adenylate cyclase studies. PG - 395-401 AB - Radioligand binding studies have previously identified a high affinity, magnesium-dependent, guanine nucleotide-sensitive binding site for corticotropin-releasing factor (CRF) in mouse spleen. In order to determine the functional nature of these CRF binding sites, we examined the effects of CRF on adenylate cyclase activity in mouse spleen homogenates. The stimulation of adenylate cyclase activity was dependent on time, tissue protein concentration, and guanine nucleotides. CRF-stimulated adenylate cyclase activity was evident in the presence of guanosine-5'-triphosphate (GTP) and its precursor guanosine-5'-diphosphate (GDP) but was not detected in the presence of the hydrolysis-resistant GTP analogs, guanyl-5'-imidodiphosphate [Gpp(NH)p] and guanosine-5'-gamma-thiotriphosphate (GTP-gamma-S). The rank order of potency for CRF analogs and fragments in stimulating adenylate cyclase activity was comparable to their affinities for CRF binding sites in mouse spleen homogenates. The putative receptor antagonist, alpha helical ovine CRF(9-41), did not stimulate adenylate cyclase activity but did attenuate the stimulation by various concentrations of rat/human CRF. In summary, these data demonstrate the functional nature of CRF receptors in mouse spleen as evidenced by CRF stimulation of cAMP production and suggest that this peptide may play a physiological role in regulating immune function. FAU - Webster, E L AU - Webster EL AD - Neuroscience Branch, National Institute on Drug Abuse, Baltimore, MD 21224. FAU - Battaglia, G AU - Battaglia G FAU - De Souza, E B AU - De Souza EB LA - eng PT - Journal Article PL - United States TA - Peptides JT - Peptides JID - 8008690 RN - 0 (Receptors, Corticotropin-Releasing Hormone) RN - 0 (Receptors, Neurotransmitter) RN - 0 (Recombinant Proteins) RN - 0 (Thionucleotides) RN - 34273-04-6 (Guanylyl Imidodiphosphate) RN - 37589-80-3 (Guanosine 5'-O-(3-Thiotriphosphate)) RN - 86-01-1 (Guanosine Triphosphate) RN - 9015-71-8 (Corticotropin-Releasing Hormone) RN - EC 4.6.1.1 (Adenylyl Cyclases) SB - IM MH - Adenylyl Cyclases/*metabolism MH - Animals MH - Brain/enzymology MH - Corticotropin-Releasing Hormone/*metabolism/*pharmacology MH - Guanosine 5'-O-(3-Thiotriphosphate) MH - Guanosine Triphosphate/analogs & derivatives/pharmacology MH - Guanylyl Imidodiphosphate/pharmacology MH - Kinetics MH - Male MH - Mice MH - Mice, Inbred C57BL MH - Receptors, Corticotropin-Releasing Hormone MH - Receptors, Neurotransmitter/*metabolism MH - Recombinant Proteins/pharmacology MH - Spleen/enzymology/*metabolism MH - Thionucleotides/pharmacology EDAT- 1989/03/01 00:00 MHDA- 1989/03/01 00:01 CRDT- 1989/03/01 00:00 PHST- 1989/03/01 00:00 [pubmed] PHST- 1989/03/01 00:01 [medline] PHST- 1989/03/01 00:00 [entrez] AID - 0196-9781(89)90049-1 [pii] AID - 10.1016/0196-9781(89)90049-1 [doi] PST - ppublish SO - Peptides. 1989 Mar-Apr;10(2):395-401. doi: 10.1016/0196-9781(89)90049-1.