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Receptors for VIP and PACAP in guinea pig cerebral cortex

Effects on cyclic AMP synthesis and characterization by 125I-VIP binding

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Abstract

Receptors for vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase-activating polypeptide (PACAP) in guinea pig cerebral cortex were characterized by (1) radioreceptor binding of 125I-labeled VIP (human/rat/porcine), and (2) cyclic AMP (cAMP) formation. Saturation analysis of 125I-VIP binding to membranes of guinea pig cerebral cortex resulted in a linear Scatchard plot, suggesting the presence of a single class of high-affinity receptor-binding sites, with a Kd of 0.63 nM and a Bmax of 77 fmol/mg protein. Various peptides from the PACAP/VIP/secretin family displaced the specific binding of 125I-VIP to guinea pig cerebrum with the relative rank order of potency: chicken VIP (cVIP) ≥ PACP38 ∼ PACAP27 ∼ guinea pig VIP (gpVIP) ≥ mammalian (human/rat/porcine) VIP (mVIP) > peptide histidine-methionine (PHM) > peptide histidine-isoleucine (PHI) > secretin. Analysis of the competition curves revealed displacement of 125I-VIP from high- and lower-affinity binding sites, with IC50 values in the picomolar and the nanomolar range, respectively. About 70% of the specific 125I-VIP-binding sites in guinea pig cerebral cortex were sensitive to Gpp(NH)p, a nonhydrolyzable analog of GTP. Pituitary adenylate cyclase-activating polypeptide 38 (PACAP38), PACAP27, cVIP, gpVIP, mVIP, PHM, and PHI stimulated cAMP production in [3H]adenine-prelabeled slices of guinea pig cerebral cortex in a concentration-dependent manner. Of the tested peptides, the most effective were PACAP38 and PACAP27, which at a 1 µM concentration produced a 17- to 19-fold rise in cAMP synthesis, increasing the nucleotide production to approx 11% conversion above the control value. The three forms of VIP (cVIP, mVIP, and gpVIP) at the highest concentration used, i.e., 3 µM, produced net increases in cAMP production in the range of 8–9% conversion, whereas 5 µM PHM and PHI, by, respectively, 6.7% and 4.9% conversion. It is concluded that cerebral cortex of guinea pig contains VPAC- type receptors positively linked to cAMP formation. In addition, the observed stronger action of PACAP (both PACAP38 and PACAP27), when compared to any form of VIP, on cAMP production in this tissue, suggests its interaction with both PAC1 and VPAC receptors.

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Authors and Affiliations

  1. Centre for Medical Biology, Polish Academy of Sciences, 93-232, Lodz, Poland

    Jolanta B. Zawilska, Agnieszka Dejda & Jerzy Z. Nowak

  2. Department of Pharmacology, Medical University of Lodz, Lodz, Poland

    Jerzy Z. Nowak

  3. Department of Pharmacodynamics, Medical University of Lodz, Lodz, Poland

    Jolanta B. Zawilska & Pawel Niewiadomski

  4. Department of Clinical Biochemistry, Sackler Faculty of Medicine, Tel Aviv University, 69978, Tel Aviv, Israel

    Illana Gozes

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  1. Jolanta B. Zawilska
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  2. Agnieszka Dejda
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  3. Pawel Niewiadomski
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  4. Illana Gozes
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  5. Jerzy Z. Nowak
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Correspondence to Jolanta B. Zawilska.

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Zawilska, J.B., Dejda, A., Niewiadomski, P. et al. Receptors for VIP and PACAP in guinea pig cerebral cortex. J Mol Neurosci 25, 215–224 (2005). https://doi.org/10.1385/JMN:25:3:215

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  • DOI: https://doi.org/10.1385/JMN:25:3:215

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