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Primary cell models that closely resemble the clinically relevant<jats:italic>in vivo<\/jats:italic>site of drug action are important translational tools in drug development. However, pharmacological studies in these models are generally very limited due to the methodology used.<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental Approach<\/jats:title><jats:p>We used a neuropeptide system to demonstrate the applicability of using highly sensitive signalling assays in primary cells. We quantified the action of pituitary adenylate cyclase\u2010activating peptide (<jats:styled-content style=\"fixed-case\">PACAP<\/jats:styled-content>)\u201038,<jats:styled-content style=\"fixed-case\">PACAP<\/jats:styled-content>\u201027 and vasoactive intestinal polypeptide in primary cultures of neurons and glia derived from rat trigeminal ganglia (<jats:styled-content style=\"fixed-case\">TG<\/jats:styled-content>), comparing our observations to transfected cells.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p><jats:styled-content style=\"fixed-case\">PACAP<\/jats:styled-content>\u2010responsive receptors in rat trigeminal neurons, glia and transfected PAC<jats:sub>1n<\/jats:sub>receptors were pharmacologically distinct.<jats:styled-content style=\"fixed-case\">PACAP<\/jats:styled-content>\u201038, but not<jats:styled-content style=\"fixed-case\">PACAP<\/jats:styled-content>\u201027, activated<jats:styled-content style=\"fixed-case\">ERK<\/jats:styled-content>in glia, while both forms stimulated cellular<jats:styled-content style=\"fixed-case\">cAMP<\/jats:styled-content>production.<jats:styled-content style=\"fixed-case\">PACAP<\/jats:styled-content>(6\u201338) also displayed cell\u2010type\u2010dependent, agonist\u2010specific, antagonism.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions and Implications<\/jats:title><jats:p>The complexity of<jats:styled-content style=\"fixed-case\">PACAP<\/jats:styled-content>pharmacology in the<jats:styled-content style=\"fixed-case\">TG<\/jats:styled-content>may help to direct, more effectively, the development of disease treatments targeting the<jats:styled-content style=\"fixed-case\">PACAP<\/jats:styled-content>receptor. We suggest that these methodologies are broadly applicable to other primary cell types of human or animal origin, and that our approach may allow more thorough characterization of ligand properties in physiologically relevant cell types.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.12541","type":"journal-article","created":{"date-parts":[[2013,12,5]],"date-time":"2013-12-05T08:47:57Z","timestamp":1386233277000},"page":"1521-1533","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":42,"title":["<scp>PACAP<\/scp>receptor pharmacology and agonist bias: analysis in primary neurons and glia from the trigeminal ganglia and transfected cells"],"prefix":"10.1111","volume":"171","author":[{"given":"C S","family":"Walker","sequence":"first","affiliation":[{"name":"School of Biological Sciences University of Auckland Auckland New Zealand"},{"name":"Centre for Brain Research University of Auckland Auckland New 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