title: Differential expression of LHRH-receptor in bovine nasal tissue and its role in deslorelin delivery.
abstract: Deslorelin, a luteinizing hormone releasing hormone (LHRH) agonist, is transported via the LHRH-receptor (LHRH-R) and exhibits regional variation as follows: inferior turbinate posterior (ITP)>medium turbinate posterior (MTP)>medium turbinate anterior (MTA) of the bovine nasal mucosa. Differential LHRH-R expression in various regions of the nose is a potential explanation for regional variation in deslorelin transport. Thus, the objective was to determine whether LHRH-R expression exhibits regional variation in bovine nasal mucosa. LHRH-R density (B(max)) and affinity constant (K(d)) were determined by saturation experiments using 0.5mg tissue in the presence of increasing amounts of I(125)-deslorelin (100-100,000 cpm) at 4 degrees C for 4h. The 50% inhibitory concentration (IC(50)) was determined by competition experiments using various amounts of unlabelled deslorelin (0.01-3000 ng) at 4 degrees C for 4h. LHRH-R mRNA and protein expressions were determined using real-time PCR and Western blot analysis, respectively. LHRH-R B(max) and K(d) varied between the regions of excised bovine nasal mucosa: ITP>MTP>MTA. The inhibition experiments yielded two IC(50) concentrations which exhibited trends similar to B(max) and K(d). Real-time PCR and Western blot analysis indicated that LHRH-R expression exhibits similar trends: ITP>MTP>MTA. We identified two deslorelin binding sites in the nasal tissues, with high affinity sites representing approximately 60-70% of the total sites available. In summary, regional differences in nasal deslorelin transport correlate with regional differences in LHRH-R expression, with LHRH-R expression, peptide binding, and transport being the highest in the inferior turbinate posterior region of the nose.
authors.affiliation: Department of Pharmaceutical Sciences, the University of Nebraska Medical Center, Omaha, NE 68198, USA.
authors.forename: Sneha
authors.initials: S
authors.lastname: Sundaram
authors.forename: Shyamal K
authors.initials: SK
authors.lastname: Roy
authors.forename: Uday B
authors.initials: UB
authors.lastname: Kompella
mesh_terms: D000818:Animals; D001692:Biological Transport; D002417:Cattle; D015870:Gene Expression; D009297:Nasal Mucosa / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D011966:Receptors, LHRH / Q000235:genetics / Q000378:metabolism*; D017329:Triptorelin Pamoate / Q000031:analogs & derivatives* / Q000378:metabolism; D014420:Turbinates / Q000378:metabolism
chemical_list: D012333:RNA, Messenger; D011966:Receptors, LHRH; D017329:Triptorelin Pamoate; C066438:deslorelin