Pituitary adenylate cyclase-activating polypeptide: a novel peptide with protean implications

Abstract

Purpose of review: The purpose of this review is to highlight the importance of pituitary adenylate cyclase-activating polypeptide in physiological processes and to describe how this peptide is becoming increasingly recognized as having a major role in the body. Since its discovery in 1989, investigators have sought to determine the site of biological activity and the function of pituitary adenylate cyclase-activating polypeptide in maintaining homeostasis.

Recent findings: Since its discovery, pituitary adenylate cyclase-activating polypeptide appears to play an important role in the regulation of processes within the central nervous system and gastrointestinal tract, as well in reproductive biology. Pituitary adenylate cyclase-activating polypeptide has been shown to regulate tumor cell growth and to regulate immune function through its effects on T lympocytes. These discoveries suggest the importance of pituitary adenylate cyclase-activating polypeptide in neuronal development, neuronal function, gastrointestinal tract function and reproduction.

Summary: Future studies will examine more closely the role of pituitary adenylate cyclase-activating polypeptide in regulation of malignantly transformed cells, as well as in regulation of immune function.

Figure 1. Amino acid model and partial gene structure of the human pituitary adenylate cyclase-activating polypeptide receptor (hPACAP-R)

(a) Model of the predicted amino acid sequence for the hPACAP-R gene showing seven transmembrane-spanning regions (boxed amino acids), potential sites for N-linked glycosylation (tridents), signal peptide cleavage site, seven highly conserved cysteine residues (triangles), and the nonhomologous rPACAP-R amino acids (letters outside the circles). Amino acid products of the alternatively spliced exons, SV-1 and SV-2, are shown in brackets with their location in the third intracellular loop indicated by the arrow. (b) Model of the partial gene structure of the hPACAP-R gene showing the consensus sequences for the intron–exon splice sites for the exons SV-1 and SV-2. Two consecutive splice sites for the SV-2 exon (a and b) give rise to two possible splice variants (SV-2a and SV-2b). Modified from [10].