Expression, pharmacological, and functional evidence for PACAP/VIP receptors in human lung

1999 ◽  
Vol 277 (1) ◽  
pp. L42-L48 ◽  
Author(s):  
Rebeca Busto ◽  
Isabel Carrero ◽  
Luis G. Guijarro ◽  
Rosa M. Solano ◽  
José Zapatero ◽  
...  

Pituitary adenylate cyclase-activating peptide (PACAP) type 1 (PAC1) and common PACAP/vasoactive intestinal peptide (VIP) type 1 and 2 (VPAC1 and VPAC2, respectively) receptors were detected in the human lung by RT-PCR. The proteins were identified by immunoblotting at 72, 67, and 68 kDa, respectively. One class of PACAP receptors was defined from125I-labeled PACAP-27 binding experiments (dissociation constant = 5.2 nM; maximum binding capacity = 5.2 pmol/mg protein) with a specificity: PACAP-27 ≈ VIP > helodermin ≈ peptide histidine-methionine (PHM) ≫ secretin. Two classes of VIP receptors were established with 125I-VIP (dissociation constants of 5.4 and 197 nM) with a specificity: VIP ≈ helodermin ≈ PACAP-27 ≫ PHM ≫ secretin. PACAP-27 and VIP were equipotent on adenylyl cyclase stimulation (EC50 = 1.6 nM), whereas other peptides showed lower potency (helodermin > PHM ≫ secretin). PACAP/VIP antagonists supported that PACAP-27 acts in the human lung through either specific receptors or common PACAP/VIP receptors. The present results are the first demonstration of the presence of PAC1 receptors and extend our knowledge of common PACAP/VIP receptors in the human lung.

1998 ◽  
Vol 21 (2) ◽  
pp. 109-120 ◽  
Author(s):  
L Bresson-Bepoldin ◽  
MC Jacquot ◽  
W Schlegel ◽  
SR Rawlings

Alternative splicing of the rat type 1 pituitary adenylate cyclase-activating polypeptide (PACAP) receptor (PVR1) produces variants that couple either to both adenylyl cyclase (AC) and phospholipase C (PLC) (PVR1 short, PVR1 hop, PVR1 hiphop), or to AC alone (PVR1 hip). We have previously shown that populations of clonal alphaT3-1 gonadotrophs express PVR1 hop and PVR1 short mRNAs, whereas clonal GH4C1 somatotrophs do not. Here we have used the single cell RT-PCR technique to investigate whether normal rat gonadotrophs and somatotrophs express PVR1 mRNA, whether a single cell co-expresses multiple splice variant forms, and whether differential PVR1 mRNA expression correlates with differences in PACAP-stimulated Ca2+ signalling. We found that individual rat gonadotrophs expressed mRNA either for PVR1 hop, for PVR1 short, or co-expressed the two forms. Although we found no differences between the splice variant(s) expressed and the characteristics of PACAP-stimulated Ca2+ responses, the expression of PVR1 mRNA is consistent with the known PACAP stimulation of the PLC system in gonadotrophs. Individual rat somatotrophs also expressed PVR1 hop or PVR1 short (but not PVR1 hip) mRNAs although these forms were never co-expressed. The expression of PVR1 mRNA in somatotrophs can explain in part the activation by PACAP of the AC system in such cells. In conclusion, the single cell RT-PCR technique was used to demonstrate expression of multiple PVR1 splice variants in single identified pituitary cells. These findings open up important questions on the role of alternative splicing in cell biology.


2019 ◽  
Vol 1863 (11) ◽  
pp. 129398 ◽  
Author(s):  
Mathilde Poujol de Molliens ◽  
Priyanka Jamadagni ◽  
Myriam Létourneau ◽  
Dominic Devost ◽  
Terence E. Hébert ◽  
...  

2000 ◽  
Vol 84 (1-2) ◽  
pp. 79-89 ◽  
Author(s):  
Magdalena Sauvage ◽  
Philippe Brabet ◽  
Florian Holsboer ◽  
Joel Bockaert ◽  
Thomas Steckler

Endocrinology ◽  
2000 ◽  
Vol 141 (3) ◽  
pp. 1158-1167 ◽  
Author(s):  
Maria Lucia Scaldaferri ◽  
Andrea Modesti ◽  
Camilla Palumbo ◽  
Salvatore Ulisse ◽  
Andrea Fabbri ◽  
...  

Reproduction ◽  
2007 ◽  
Vol 134 (2) ◽  
pp. 281-292 ◽  
Author(s):  
Marzia Barberi ◽  
Barbara Muciaccia ◽  
Maria Beatrice Morelli ◽  
Mario Stefanini ◽  
Sandra Cecconi ◽  
...  

Pituitary adenylate cyclase-activating polypeptide (PACAP) and vasoactive intestinal polypeptide (VIP) positively affect several parameters correlated with the ovulatory process. PACAP is transiently expressed in rat preovulatory follicles, while VIP is present in nerve fibres at all stages of development. These two peptides act by interacting with three types of receptors: PACAP type I receptor (PAC1-R), which binds with higher affinity to PACAP, and two VIP receptors (VPAC1-R and VPAC2-R), which bind to PACAP and VIP with equal affinity. The aim of the present study was to characterise the PACAP/VIP/receptor system in the mouse ovary. Results obtained by RT-PCR, immunohistochemistry and in situ hybridisation showed that PACAP was transiently expressed in granulosa cells of preovulatory follicles after human chorionic gonadotrophin (hCG) stimulation, while VIP mRNA was never observed. All the receptors were present in 22-day-old untreated mice. In preovulatory follicles, PAC1-R was expressed both in granulosa cells and in residual ovarian tissue but was stimulated by hCG mainly in granulosa cells; VPAC2-R was present in both the cell compartments and was only mildly stimulated; VPAC1-R was present mainly in the residual ovarian tissue and was downregulated by hCG. PACAP and VIP were equipotent in inhibiting apoptosis in granulosa cells, confirming the presence of functional PACAP/VIP receptors. The contemporary induction by hCG of PACAP and PAC1-R in granulosa cells of preovulatory follicles suggests that, also in mouse ovary, PACAP may play a significant role around the time of ovulation. Moreover, the presence of PACAP/VIP receptors in the untreated ovary suggests a possible role for PACAP and VIP during follicle development.


1998 ◽  
Vol 865 (1 VIP, PACAP, A) ◽  
pp. 82-91 ◽  
Author(s):  
YONG-JIANG CAO ◽  
ELZBIETA KOJRO ◽  
MAREK JASIONOWSKI ◽  
LESZEK LANKIEWICZ ◽  
ZBIGNIEW GRZONKA ◽  
...  

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