Bombesin receptors (version 2019.4) in the IUPHAR/BPS Guide to Pharmacology Database

Mammalian bombesin (Bn) receptors comprise 3 subtypes: BB1, BB2, BB3 (nomenclature recommended by the NC-IUPHAR Subcommittee on bombesin receptors, [109]). BB1 and BB2 are activated by the endogenous ligands gastrin-releasing peptide (GRP), neuromedin B (NMB) and GRP-(18-27). bombesin is a tetradecapeptide, originally derived from amphibians. The three Bn receptor subtypes couple primarily to the Gq/11 and G12/13 family of G proteins [109]. Each of these receptors is widely distributed in the CNS and peripheral tissues [73, 109, 236, 265, 226, 348]. Activation of BB1 and BB2 receptors causes a wide range of physiological/pathophysiogical actions, including the stimulation of normal and neoplastic tissue growth, smooth-muscle contraction, feeding behavior, secretion and many central nervous system effects including regulation of circadian rhythm and mediation of pruritus [112, 113, 109, 115, 116, 155, 189, 236]. A physiological role for the BB3 receptor has yet to be fully defined although recently studies suggest an important role in glucose and insulin regulation, metabolic homeostasis, feeding, regulation of body temperature, obesity, diabetes mellitus and growth of normal/neoplastic tissues [73, 157, 203, 332]

Bombesin receptors in GtoPdb v.2021.2

Mammalian bombesin (Bn) receptors comprise 3 subtypes: BB1, BB2, BB3 (nomenclature recommended by the NC-IUPHAR Subcommittee on bombesin receptors, [115]). BB1 and BB2 are activated by the endogenous ligands neuromedin B (NMB), gastrin-releasing peptide (GRP), and GRP-(18-27). bombesin is a tetra-decapeptide, originally derived from amphibians. The three Bn receptor subtypes couple primarily to the Gq/11 and G12/13 family of G proteins [115]. Each of these receptors is widely distributed in the CNS and peripheral tissues [78, 115, 249, 278, 237, 362]. Activation of BB1 and BB2 receptors causes a wide range of physiological/pathophysiogical actions, including the stimulation of normal and neoplastic tissue growth, smooth-muscle contraction, gastrointestinal motility, feeding behavior, secretion and many central nervous system effects including regulation of circadian rhythm, body temperature control, sighing and mediation of pruritus [149, 202, 244, 115, 196, 249, 306, 68, 34, 332]. A physiological role for the BB3 receptor has yet to be fully defined although recently studies suggest an important role in glucose and insulin regulation, metabolic homeostasis, feeding, regulation of body temperature, obesity, diabetes mellitus and growth of normal/neoplastic tissues [148, 78, 162, 214, 346, 200]. Bn receptors are one of the most frequently overexpressed receptors in cancers and are receiving increased attention for their roles in tumor growth, as well as for tumour imaging and for receptor targeted cytotoxicity [202, 276, 8, 161]

Bombesin receptors in GtoPdb v.2023.1

Mammalian bombesin (Bn) receptors comprise 3 subtypes: BB1, BB2, BB3 (nomenclature recommended by the NC-IUPHAR Subcommittee on bombesin receptors, [117, 4]). BB1 and BB2 are activated by the endogenous ligands neuromedin B (NMB), gastrin-releasing peptide (GRP), and GRP-(18-27). bombesin is a tetra-decapeptide, originally derived from amphibians and structurally closely related to GRP. The three Bn receptor subtypes couple primarily to the Gq/11 and G12/13 family of G proteins [117]. Each of these receptors is widely distributed in the CNS and peripheral tissues [80, 117, 261, 290, 248, 375, 114, 164, 165]. Activation of BB1 and BB2 receptors causes a wide range of physiological/pathophysiogical actions, including the stimulation of normal and neoplastic tissue growth, smooth-muscle contraction, respiration, gastrointestinal motility, feeding behavior, secretion and many central nervous system effects including regulation of circadian rhythm, body temperature control, sighing, behavioral disorders and mediation of pruritus [153, 211, 255, 117, 205, 261, 318, 70, 35, 345, 212, 36]. BB3 is an orphan receptor, although some propose it is constitutively active [330]. BB3 receptor knockout studies show it has important roles in glucose and insulin regulation, metabolic homeostasis, feeding, regulation of body temperature, obesity, diabetes mellitus and growth of normal/neoplastic tissues [152, 80, 168, 224, 359, 209]. Bn receptors are one of the most frequently overexpressed receptors in cancers and are receiving increased attention for their roles in tumor growth, as well as for tumour imaging and for receptor-targeted cytotoxicity [211, 288, 9, 167, 171, 172, 135, 202]. Bn receptors are also receiving attention because they are one of the primary neurotransmitters for pruritus [36, 127, 35, 318]

Class A Orphans in GtoPdb v.2023.1

Table 1 lists a number of putative GPCRs identified by NC-IUPHAR [161], for which preliminary evidence for an endogenous ligand has been published, or for which there exists a potential link to a disease, or disorder. These GPCRs have recently been reviewed in detail [121]. The GPCRs in Table 1 are all Class A, rhodopsin-like GPCRs. Class A orphan GPCRs not listed in Table 1 are putative GPCRs with as-yet unidentified endogenous ligands.Table 1: Class A orphan GPCRs with putative endogenous ligands GPR3GPR4GPR6GPR12GPR15GPR17GPR20 GPR22GPR26GPR31GPR34GPR35GPR37GPR39 GPR50GPR63GPR65GPR68GPR75GPR84GPR87 GPR88GPR132GPR149GPR161GPR183LGR4LGR5 LGR6MAS1MRGPRDMRGPRX1MRGPRX2P2RY10TAAR2 In addition the orphan receptors GPR18, GPR55 and GPR119 which are reported to respond to endogenous agents analogous to the endogenous cannabinoid ligands have been grouped together (GPR18, GPR55 and GPR119)

Class A Orphans (version 2020.5) in the IUPHAR/BPS Guide to Pharmacology Database

Table 1 lists a number of putative GPCRs identified by NC-IUPHAR [194], for which preliminary evidence for an endogenous ligand has been published, or for which there exists a potential link to a disease, or disorder. These GPCRs have recently been reviewed in detail [150]. The GPCRs in Table 1 are all Class A, rhodopsin-like GPCRs. Class A orphan GPCRs not listed in Table 1 are putative GPCRs with as-yet unidentified endogenous ligands.Table 1: Class A orphan GPCRs with putative endogenous ligands GPR3 GPR4 GPR6 GPR12 GPR15 GPR17 GPR20 GPR22 GPR26 GPR31 GPR34 GPR35 GPR37 GPR39 GPR50 GPR63 GRP65 GPR68 GPR75 GPR84 GPR87 GPR88 GPR132 GPR149 GPR161 GPR183 LGR4 LGR5 LGR6 MAS1 MRGPRD MRGPRX1 MRGPRX2 P2RY10 TAAR2 In addition the orphan receptors GPR18, GPR55 and GPR119 which are reported to respond to endogenous agents analogous to the endogenous cannabinoid ligands have been grouped together (GPR18, GPR55 and GPR119)

Class A Orphans in GtoPdb v.2022.3

Table 1 lists a number of putative GPCRs identified by NC-IUPHAR [161], for which preliminary evidence for an endogenous ligand has been published, or for which there exists a potential link to a disease, or disorder. These GPCRs have recently been reviewed in detail [121]. The GPCRs in Table 1 are all Class A, rhodopsin-like GPCRs. Class A orphan GPCRs not listed in Table 1 are putative GPCRs with as-yet unidentified endogenous ligands.Table 1: Class A orphan GPCRs with putative endogenous ligands GPR3GPR4GPR6GPR12GPR15GPR17GPR20 GPR22GPR26GPR31GPR34GPR35GPR37GPR39 GPR50GPR63GPR65GPR68GPR75GPR84GPR87 GPR88GPR132GPR149GPR161GPR183LGR4LGR5 LGR6MAS1MRGPRDMRGPRX1MRGPRX2P2RY10TAAR2 In addition the orphan receptors GPR18, GPR55 and GPR119 which are reported to respond to endogenous agents analogous to the endogenous cannabinoid ligands have been grouped together (GPR18, GPR55 and GPR119)

Class A Orphans in GtoPdb v.2021.3

Table 1 lists a number of putative GPCRs identified by NC-IUPHAR [161], for which preliminary evidence for an endogenous ligand has been published, or for which there exists a potential link to a disease, or disorder. These GPCRs have recently been reviewed in detail [121]. The GPCRs in Table 1 are all Class A, rhodopsin-like GPCRs. Class A orphan GPCRs not listed in Table 1 are putative GPCRs with as-yet unidentified endogenous ligands.Table 1: Class A orphan GPCRs with putative endogenous ligands GPR3GPR4GPR6GPR12GPR15GPR17GPR20 GPR22GPR26GPR31GPR34GPR35GPR37GPR39 GPR50GPR63GRP65GPR68GPR75GPR84GPR87 GPR88GPR132GPR149GPR161GPR183LGR4LGR5 LGR6MAS1MRGPRDMRGPRX1MRGPRX2P2RY10TAAR2 In addition the orphan receptors GPR18, GPR55 and GPR119 which are reported to respond to endogenous agents analogous to the endogenous cannabinoid ligands have been grouped together (GPR18, GPR55 and GPR119)

Class A Orphans (version 2019.4) in the IUPHAR/BPS Guide to Pharmacology Database

Table 1 lists a number of putative GPCRs identified by NC-IUPHAR [191], for which preliminary evidence for an endogenous ligand has been published, or for which there exists a potential link to a disease, or disorder. These GPCRs have recently been reviewed in detail [148]. The GPCRs in Table 1 are all Class A, rhodopsin-like GPCRs. Class A orphan GPCRs not listed in Table 1 are putative GPCRs with as-yet unidentified endogenous ligands.Table 1: Class A orphan GPCRs with putative endogenous ligands GPR3GPR4GPR6GPR12GPR15GPR17GPR20 GPR22GPR26GPR31GPR34GPR35GPR37GPR39 GPR50GPR63GRP65GPR68GPR75GPR84GPR87 GPR88GPR132GPR149GPR161GPR183LGR4LGR5 LGR6MAS1MRGPRDMRGPRX1MRGPRX2P2RY10TAAR2 In addition the orphan receptors GPR18, GPR55 and GPR119 which are reported to respond to endogenous agents analogous to the endogenous cannabinoid ligands have been grouped together (GPR18, GPR55 and GPR119)

Genome variation and population structure among 1142 mosquitoes of the African malaria vector species Anopheles gambiae and Anopheles coluzzii

Mosquito control remains a central pillar of efforts to reduce malaria burden in sub-Saharan Africa. However, insecticide resistance is entrenched in malaria vector populations, and countries with a high malaria burden face a daunting challenge to sustain malaria control with a limited set of surveillance and intervention tools. Here we report on the second phase of a project to build an open resource of high-quality data on genome variation among natural populations of the major African malaria vector species Anopheles gambiae and Anopheles coluzzii. We analyzed whole genomes of 1142 individual mosquitoes sampled from the wild in 13 African countries, as well as a further 234 individuals comprising parents and progeny of 11 laboratory crosses. The data resource includes high-confidence single-nucleotide polymorphism (SNP) calls at 57 million variable sites, genome-wide copy number variation (CNV) calls, and haplotypes phased at biallelic SNPs. We use these data to analyze genetic population structure and characterize genetic diversity within and between populations. We illustrate the utility of these data by investigating species differences in isolation by distance, genetic variation within proposed gene drive target sequences, and patterns of resistance to pyrethroid insecticides. This data resource provides a foundation for developing new operational systems for molecular surveillance and for accelerating research and development of new vector control tools. It also provides a unique resource for the study of population genomics and evolutionary biology in eukaryotic species with high levels of genetic diversity under strong anthropogenic evolutionary pressures

Resistance to pirimiphos-methyl in West African Anopheles is spreading via duplication and introgression of the Ace1 locus

Vector population control using insecticides is a key element of current strategies to prevent malaria transmission in Africa. The introduction of effective insecticides, such as the organophosphate pirimiphos-methyl, is essential to overcome the recurrent emergence of resistance driven by the highly diverse Anopheles genomes. Here, we use a population genomic approach to investigate the basis of pirimiphos-methyl resistance in the major malaria vectors Anopheles gambiae and A. coluzzii. A combination of copy number variation and a single non-synonymous substitution in the acetylcholinesterase gene, Ace1, provides the key resistance diagnostic in an A. coluzzii population from Coˆte d’Ivoire that we used for sequence-based association mapping, with replication in other West African populations. The Ace1 substitution and duplications occur on a unique resistance haplotype that evolved in A. gambiae and introgressed into A. coluzzii, and is now common in West Africa primarily due to selection imposed by other organophosphate or carbamate insecticides. Our findings highlight the predictive value of this complex resistance haplotype for phenotypic resistance and clarify its evolutionary history, providing tools to for molecular surveillance of the current and future effectiveness of pirimiphos-methyl based interventions