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Pituitary Adenylate Cyclase-Activating Polypeptide pp 227–249Cite as

PACAP: An ‘Emergency Response’ Co-Transmitter in the Adrenal Medulla

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Part of the book series: Endocrine Updates ((ENDO,volume 20))

Abstract

PACAP was named based on its presumed function as a hypothalamohypophysial releasing hormone, in turn based on its original characterization in a biochemical-cellular screen for just such a factor. In the late 1980s, Arimura and colleagues decided on an innovative and systematic approach to finding the few remaining factors needed to complete the complement of molecules released from the hypothalamus into the portal circulation of the pituitary and controlling the secretion of ACTH, LH, FSH, prolactin, growth hormone, and thyroid hormone from the anterior pituitary. Evidence existed for as-yet uncharacterized FSH and PRL releasing hormones, and for factors regulating the non-endocrine folliculostellate cells of the anterior pituitary. Since CRF, LH-RH, GH-RH, and TRH all act by increasing cyclic AMP generation in corticotrophs, gonadotrophs, somatotrophs and thyrotrophs, respectively, it stood to reason that the elusive FSH-RH and PRL-RH, if they existed, should also elevate cyclic AMP in gonadotrophs and lactotrophs. Accordingly the Arimura group screened hypothalamic extracts for a new peptide that could do this. PACAP38 was identified based on its ability to elevate cyclic AMP levels and release pituitary hormones in superfused pituitaries, and PACAP27 and PACAP38 were found to be abundantly expressed in hypothalamus and extrahypothalamic locations shortly thereafter (Arimura, 1998). The name stuck, yet PACAP does not appear to be the still-at-large FSH-RH or PRL-RH. In fact, its actions at the pituitary (see accompanying review by Arimura) have still not been comfortably placed in a physiological context. In the meanwhile, the discovery of PACAP stimulated much additional work on the extrapituitary distribution and potential physiological role of this peptide, summarized in authoritative reviews (Arimura, 1998; Vaudry et al, 2000). One area of recent advance not emphasized in that review is the role of PACAP in the adrenal medulla, where the function of PACAP in the splanchnic nerve represents one of the best-studied exemplars of classical neurotransmitter/neuropeptide co-transmission in the entire nervous system. This chapter attempts to rectify this gap in the review literature, and ends by chronicling recent developments culminating in the firm establishment of PACAP as a co-transmitter, with acetycholine, in the adrenal medulla. PACAP’s role as an adrenomedullary co-transmitter may well be prototypical for an important general role for neuropeptides in synaptic transmission: that of providing a ‘stress response’ or ‘emergency response’ capability to a synapse that functions adequately in the short-term using a classical neurotransmitter, but requires a peptide co-transmitter for sustained secretory activity under paraphysiological conditions.

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Authors and Affiliations

  1. Section on Molecular Neuroscience, National Institute of Mental Health, Bethesda, 20892, MD, USA

    C. Hamelink & L. E. Eiden

  2. Institute of Anatomy and Cell Biology, Philipps-Universität, Marburg, D-35033, Germany

    E. Weihe

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  1. C. Hamelink
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  1. European Institute for Peptide Research, INSERM Unit 413, University of Rouen, Mont-Saint-Aignan, France

    Hubert Vaudry

  2. US Japan Biomedial Research Laboratories, Tulane University, Belle Chasse, Louisiana, USA

    Akira Arimura

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Hamelink, C., Weihe, E., Eiden, L.E. (2003). PACAP: An ‘Emergency Response’ Co-Transmitter in the Adrenal Medulla. In: Vaudry, H., Arimura, A. (eds) Pituitary Adenylate Cyclase-Activating Polypeptide. Endocrine Updates, vol 20. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-0243-2_10

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