Disease relevance of ADCYAP1R1

• G-protein-coupled receptor kinase 3- and protein kinase C-mediated desensitization of the PACAP receptor type 1 in human Y-79 retinoblastoma cells [1].
• PACAP(6-38) is a PACAP receptor antagonist for breast cancer cells [2].
• A weak PACAP mRNA and PACAP receptor mRNA expression was detected in only 3 of 16 meningiomas [3].
• In the 16 gliomas studied (including two oligodendrogliomas and two ependymomas), PACAP mRNA was identified in 13 samples and PACAP receptor mRNA in 15 samples [3].
• Systematic deletion of the first 13 amino acids of both PACAP was tested by evaluating their ability to occupy the specific and selective PACAP receptor of human neuroblastoma NB-OK-1 cell membranes and to stimulate adenylate cyclase or, when inactive per se, to inhibit PACAP-stimulated adenylate cyclase activity [4].

High impact information on ADCYAP1R1

• Studies of the genes encoding the PACAP precursor and the type I PACAP receptor provide information on the control of PACAP gene expression and on the relationship between the structure of the receptor subtypes and the activation of various signal transduction pathways [5].
• We report here the cloning, characterization, and chromosomal location of the gene encoding the human type I VIP receptor (HVR1), also termed the type II PACAP receptor [6].
• We previously described alternative splicing of the region encoding the third intracellular loop of the PACAP receptor generating six isoforms with differential signal transduction properties (Spengler, D., Waeber, C., Pantaloni, C., Holsboer, F., Bockaert, J., Seeburg, P. H., and Journot, L. (1993) Nature 365, 170-175) [7].
• The PACAP receptor was solubilized from bovine brain membranes with digitonin and purified 30-fold by the combination of DEAE-Toyopearl and hydroxylapatite chromatographic analyses [8].
• However, none of the VIP/PACAP receptor proteins has been visualized individually in human tumors [9].

Biological context of ADCYAP1R1

• A yeast artificial chromosome containing ADCYAP1R1 was identified in the CEPH "B" Mega-YAC library [10].
• This YAC includes two highly polymorphic dinucleotide repeat sequences that will facilitate genetic studies of the contribution of ADCYAP1R1 in disease states of the central nervous and neuroendocrine systems [10].
• The sequence of the frog receptor should thus prove useful to decipher the structure-activity relationships of the VIP/PACAP receptor family [11].
• An amphibian VIP/PACAP receptor complementary DNA (cDNA) has been cloned and characterized from a frog (Rana ridibunda) pituitary cDNA library [11].
• These results demonstrate the expression of PACAPR messenger RNA in granulosa cells of growing follicles and of preovulatory follicles stimulated by gonadotropins, and suggest that PACAP may play a role in the growth of developing follicles and in ovulation as an autocrine/paracrine factor [12].

Anatomical context of ADCYAP1R1

• PAC1-R is the predominant PACAP receptor found in fetuses, and both PAC1-R and VPAC1-R are expressed in the mature cerebellum [13].
• Northern blot analysis revealed that PACAP receptor mRNAs were expressed mainly in the brain and widely distributed in the central nervous system [14].
• RNA transcripts for all three PACAP receptor types are found in human heart, brain and adipose tissue, while PACAP/VIP R-2 is the only one of these three receptor types that is expressed in the pancreas and skeletal muscle [15].
• The expression of the PACAP receptor was demonstrated by direct binding studies and/or by the relative potency of PACAPs and VIP to stimulate adenylate cyclase activity in 16 of the 22 tumors and in all the cell lines [16].
• The major cell types expressing PACAPR messenger RNA were granulosa cells of large preantral follicles [12].

Associations of ADCYAP1R1 with chemical compounds

• This is the first localization of all of the VIP/PACAP receptor subtypes in human formalin-fixed, paraffin-embedded tissues [9].
• The contraction of IAS by PACAP is speculated to occur via the activation of PACAP receptor at the substance P-containing nerve terminals [17].

Regulatory relationships of ADCYAP1R1

• VIP/PACAP receptor activation stimulates the production of [cAMP]i and [Ca2+]i by coupling to independent G-protein subunits, although agonist potencies for the different transduction pathways appear to differ [18].

Other interactions of ADCYAP1R1

• Pituitary adenylate cyclase-activating polypeptide (PACAP) and PACAP-receptor type 1 expression in rat and human placenta [19].
• Two subtypes of PACAP receptor mRNAs, pituitary adenylate cyclase-activating polypeptide-specific receptor (PAC1-R) and pituitary adenylate cyclase-activating polypeptide/vasoactive intestinal polypeptide mutual receptor (VPAC2-R), are actively expressed in the arcuate nucleus of the hypothalamus, where POMC cell bodies are located [20].
• This previously allowed us to develop modified secretin and GRF derivatives as high affinity and highly selective VIP1/PACAP receptor ligands [21].
• Transactivation of the type I PACAP receptor gene by Zac1 and p53 points to a subtle balance between death promoting and protective mechanisms [22].
• Induction of type I PACAP receptor expression by the new zinc finger protein Zac1 and p53 [22].

Analytical, diagnostic and therapeutic context of ADCYAP1R1

• RT-PCR analysis revealed the widespread distribution of this frog VIP/PACAP receptor in peripheral tissues [11].
• This was accomplished by comparing catecholamine secretion in the presence or absence of cholinergic and the VIP and PACAP receptor antagonists during different levels of electrical stimulation [23].
• In cultured rat Müller cells, the expression of PACAP receptor (PAC1-R) was assessed with immunohistochemistry using a PAC1-R-specific antiserum [24].
• The distribution of the transcripts of PACAP receptor genes has been studied in various tissues using in situ hybridization [25].
• METHODS: Expression of PACAP receptor mRNA was examined by reverse transcription polymerase chain reaction (RT-PCR) [26].

References