Receptor-induced phasic activity of newborn mouse bladders is inhibited by protein kinase C and involves T-type Ca2+
Mari Ekman1, Karl-Erik Andersson, Anders Arner
1Department of Experimental Medical Science, Lund University, Lund, Sweden.
Objective:
To investigate the mechanisms involved in the phasic contractile activity after muscarinic receptor activation of newborn urinary bladders and to compare neonatal and adult bladders.
Materials And Methods:
Detrusor muscle strips were isolated from newborn mice (aged 0-2 days) and compared with preparations from adult mice (aged 10-12 weeks). The effects of an activator (phorbol 12,13-dibutyrate, PDBu) and an inhibitor (GF109203X) of protein kinase C (PKC) on contractions were investigated. T-type Ca2+ channels were blocked with NiCl2.
Results:
The newborn urinary bladders responded with prominent phasic contractile activity in response to carbachol (1 microM). GF109203X (3 microM) reduced carbachol-induced force by approximately 60% in the newborn, compared with 30% in the adult. PDBu (1 microM) enhanced the muscarinic receptor-mediated contraction in adult bladder muscle, whereas it completely abolished the responses in the newborn. There was no inhibition after activation with depolarization (high-K+) or purinergic agonists (ATP, alpha,beta-methylene ATP). NiCl2 (>30 microM) inhibited the peak responses to carbachol in the newborn and at 300 microm it completely abolished the phasic contractile response. The responses of the adult bladder muscle were only marginally affected by NiCl2.
Conclusions:
Muscarinic receptor stimulation recruits the PKC signalling pathway in both the adult and neonatal urinary bladder. Potent PKC activation is inhibitory on carbachol-induced activation in the newborn and stimulatory in the adult bladder. Furthermore, muscarinic receptor stimulation activates T-type Ca2+ channels in the newborn, but not the adult bladder.
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