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Pituitary Adenylate Cyclase-Activating Polypeptide Potentiation of Ca²⁺ Entry via Protein Kinase C and A Pathways in Melanotrophs of the Pituitary Pars Intermedia of Rats¹

Department of Physiology, University of Occupational and Environmental Health, School of Medicine, Kitakyusyu 807, Japan

Address all correspondence and requests for reprints to: Hiroshi Yamashita, M.D., Ph.D., Department of Physiology, University of Occupational and Environmental Health, Kitakyusyu 807, Japan.

Pituitary adenylate cyclase-activating polypeptide (PACAP) has been reported to stimulate melanotroph secretion, and PACAP-like immunoreactivity and expression of PACAP type I receptor messenger RNA have been identified in the pituitary pars intermedia (PI). The present study showed that PACAP messenger RNA is also expressed in the PI. To examine the mechanism of PACAP action in the PI, cytosolic Ca²⁺ concentrations ([Ca²⁺]_i) and ionic currents were measured in acutely dissociated rat melanotrophs. In about 40% of the melanotrophs studied, PACAP induced an increase in [Ca²⁺]_i, which was suppressed by extracellular Ca²⁺ removal; extracellular Na⁺ replacement; the blocker of L-type Ca²⁺ channels, nicardipine; or the secreto-inhibitory neurotransmitter, dopamine. The PACAP-induced [Ca²⁺]_i increase was mimicked by activators of protein kinase A (PKA) and protein kinase C (PKC), Sp-diastereomer of cAMP and 1-oleoyl-2-acetyl-sn-glycerol, and was reduced by inhibitors of PKA and PKC, Rp-diastereomer of cAMP and staurosporine. Patch-clamp analysis revealed that PACAP caused inward currents with a reversal potential of -0.8 mV and facilitated voltage-dependent Ba²⁺ currents. It further revealed that PACAP-induced inward currents were mimicked by 1-oleoyl-2-acetyl-sn-glycerol and inhibited by staurosporine, and that Sp-diastereomer of cAMP facilitated Ba²⁺ currents.

These results suggest that PACAP potentiates Ca²⁺ entry mechanisms of rat melanotrophs by activation of nonselective cation channels via PKC and facilitation of voltage-dependent Ca²⁺ channels via PKA.

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