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Pituitary adenylate cyclase‐activating polypeptide may function as a neuromodulator in guinea‐pig adrenal medulla
Author(s) -
Inoue M.,
Fujishiro N.,
Ogawa K.,
Muroi M.,
Sakamoto Y.,
Imanaga I.,
Shioda S.
Publication year - 2000
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1111/j.1469-7793.2000.00473.x
Subject(s) - muscarine , adrenal medulla , medicine , endocrinology , forskolin , chemistry , secretion , adrenal gland , protein kinase a , biology , catecholamine , receptor , muscarinic acetylcholine receptor , biochemistry , phosphorylation , stimulation
1 The role of pituitary adenylate cyclase‐activating polypeptide (PACAP) in catecholamine secretion from dissociated adrenal chromaffin cells of the guinea‐pig was investigated using amperometry, the patch clamp technique and immunochemistry. 2 Pretreatment of adrenal chromaffin cells with 0·3–10 n m PACAP for 2 min resulted in enhancement of nicotine‐ and muscarine‐induced secretions in either the presence of external Ca 2+ ions or nominally Ca 2+ ‐free solution, with no change in basal secretion or the holding current at −60 mV in most of the cells tested. 3 Pretreatment with PACAP augmented the muscarine‐induced non‐selective cation current, but did not affect the muscarine‐induced outward current or nicotine‐induced current. 4 PACAP‐induced enhancement of nicotine‐ and muscarine‐induced secretions was suppressed by the simultaneous application of PACAP and the protein kinase inhibitors 100 μ m HA1004 or 2 μ m H89. 5 Application of forskolin enhanced both muscarine‐ and nicotine‐induced secretions, whereas application of a phorbol ester augmented the nicotine‐induced secretion, but suppressed the muscarine‐induced secretion in a reversible manner. 6 Immunohistochemical analysis of adrenal medullae revealed that PACAP‐like immunoreactivity was present in nerve fibres surrounding putative chromaffin cells. PAC1R‐like immunoreactivity was distributed diffusely in the plasma membrane, whereas nicotinic ACh receptor‐like immunoreactivity was concentrated at the plasma membrane near the nucleus, where the synapses were mainly localized. 7 These observations suggest that PACAP in the guinea‐pig adrenal medulla functions as a neuromodulator to facilitate ACh‐induced secretion through a cAMP‐protein kinase A‐dependent pathway.