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Perspective on the role of P2X‐purinoceptor activation in human vas deferens contractility
Author(s) -
Amobi Nnaemeka I. B.,
Guillebaud John,
Smith I. Christopher H.
Publication year - 2012
Publication title -
experimental physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.925
H-Index - 101
eISSN - 1469-445X
pISSN - 0958-0670
DOI - 10.1113/expphysiol.2011.063206
Subject(s) - iberiotoxin , purinergic receptor , apamin , vas deferens , medicine , channel blocker , endocrinology , contractility , thapsigargin , chemistry , agonist , bk channel , p2y receptor , muscle contraction , potassium channel blocker , potassium channel , receptor , biology , calcium
The contractile actions of α,β‐methylene ATP (α,β‐meATP) and ATP and the effects of K + channel blockers in longitudinal and circular muscles of human vas deferens were investigated with a view to clarifying the functional importance of P2X 1 ‐purinoceptor activation and K + channels in modulating contractility of the tissues. The results provide an experiment‐based perspective for resolving differing reports on purinergic activation of the tissues and uncertain roles of large‐conductance Ca 2+ ‐activated K + (BK Ca ) and voltage‐gated delayed rectifier K + (K V ) channels. α,β‐Methylene ATP (3–100 μ m ) evoked suramin‐sensitive contractions of longitudinal muscle but rarely of circular muscle. ATP (0.1–3 m m ) less reliably activated only longitudinal muscle contractions. These were enhanced by ARL 67156 (100 μ m ), but a different ectonucleotidase inhibitor, POM 1, was ineffective. Both muscle types were unresponsive to ADP‐βS (100 μ m ), a P2Y‐purinoceptor agonist. Longitudinal muscle contractions in response to α,β‐meATP were enhanced by FPL 64176 (1 μ m ), an L‐type Ca 2+ agonist, TEA (1 m m ), a non‐specific K + channel blocker, 4‐aminopyridine (0.3 m m ), a selective blocker of K V channels, and iberiotoxin (0.1 μ m ), a selective blocker of BK Ca channels. Quiescent circular muscles responded to α,β‐meATP reliably in the presence of FPL 64176 or iberiotoxin. Apamin (0.1 μ m ), a selective blocker of small conductance Ca 2+ ‐activated K + (SK Ca ) channels had no effect in both muscle types. Y‐27632 (1–10 μ m ) reduced longitudinal muscle contractions in response to α,β‐meATP, suggesting involvement of Rho‐kinase‐dependent contractile mechanisms. The results indicate that P2X 1 ‐purinoceptor stimulation elicits excitatory effects that: (a) lead to longitudinal muscle contraction and secondary activation of 4‐aminopyridine‐sensitive (K V ) and iberiotoxin‐sensitive (BK Ca ) K + channels; and (b) are subcontractile in circular muscle due to ancillary activation of BK Ca channels. The novel finding of differential action by P2X 1 ‐purinoceptor agonists in the muscle types has functional implication in terms of the purinergic contribution to overall contractile function of human vas deferens. The modulatory effects of K V and BK Ca channels following P2X 1 ‐purinoceptor activation may be pivotal in providing the crucial physiological mechanism that ensures temporal co‐ordination of longitudinal and circular muscle contractility.