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Carotid body afferent activity stimulation by PACAP is mediated through PKC pathway
Author(s) -
Roy Arijit,
Wilson Richard James Alfred
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.897.7
Subject(s) - protein kinase c , chelerythrine , stimulation , carotid body , endocrinology , chemistry , medicine , receptor , adenylate kinase , protein kinase a , vasoactive intestinal peptide , cyclase , pituitary adenylate cyclase activating peptide , signal transduction , kinase , biology , neuropeptide , biochemistry
Pituitary adenylate cyclase‐activating polypeptide (PACAP) but not vasoactive intestinal peptide (VIP) injected into the common carotid artery stimulates ventilation, suggesting activation of PAC1 receptors within the primary peripheral respiratory chemoreceptor, the carotid body (CB). Possible biochemical pathways downstream of the PAC1 receptor include G‐proteins activation of (a) PLC which stimulates protein kinase C (PKC) and (b) cAMP which stimulates protein kinase A (PKA). Here we elucidate the relative importance of PKC and PKA in mediating PACAP's effects on carotid sinus nerve activity. We used an ex‐vivo artificially – perfused rat CB preparation and measured integrated CSN activity during normoxia (PO 2 ≃ 100 Torr/PCO 2 ≃ 35 Torr) and tested effects of PACAP 1–38 (100 nM) alone and against a background of : (a) PKC inhibitors – GF 109203X (GF;10 μM) and Chelerythrine chloride (CC;20 μM) and (b) PKA inhibitor – H89 (10 μM). We demonstrate PACAP stimulates CSN activity in a biphasic manner, with an initial transient stimulatory phase, followed by a steady‐state phase. PKC inhibitors, GF and CC (n=6) reduced both peak and steady state PACAP responses by over 50%. The PKA inhibitor H89 had no effect on the transient phase but reduced the steady state by 17%. In conclusion, PACAP induced stimulation of CSN activity is mediated primarily through a PLC‐IP 3 ‐ PKC, not a cAMP‐PKA pathway.