Perspective on the role of P2X-purinoceptor activation in human vas deferens contractility.
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 μm) evoked suramin-sensitive contractions of longitudinal muscle but rarely of circular muscle. ATP (0.1-3 mm) less reliably activated only longitudinal muscle contractions. These were enhanced by ARL 67156 (100 μm), but a different ectonucleotidase inhibitor, POM 1, was ineffective. Both muscle types were unresponsive to ADP-βS (100 μm), a P2Y-purinoceptor agonist. Longitudinal muscle contractions in response to α,β-meATP were enhanced by FPL 64176 (1 μm), an L-type Ca(2+) agonist, TEA (1 mm), a non-specific K(+) channel blocker, 4-aminopyridine (0.3 mm), a selective blocker of K(V) channels, and iberiotoxin (0.1 μm), 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 μm), a selective blocker of small conductance Ca(2+)-activated K(+) (SK(Ca)) channels had no effect in both muscle types. Y-27632 (1-10 μm) 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.
King’s College London, Guys Campus, London SE1 1UL, UK. nnaemeka.amobi@btinternet.com
Nnaemeka I B
NI
Amobi
John
J
Guillebaud
I Christopher H
IC
Smith
D015761:4-Aminopyridine / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000494:pharmacology / Q000502:physiology; D000577:Amides / Q000494:pharmacology; D001030:Apamin / Q000494:pharmacology; D002120:Calcium Channel Agonists / Q000494:pharmacology; D020746:Calcium Channels, L-Type / Q000187:drug effects; D006801:Humans; D051036:Large-Conductance Calcium-Activated Potassium Channels / Q000502:physiology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology*; D009638:Norepinephrine / Q000494:pharmacology; D010455:Peptides / Q000494:pharmacology; D026902:Potassium Channel Blockers / Q000494:pharmacology; D024642:Potassium Channels, Voltage-Gated / Q000502:physiology; D058911:Purinergic P2X Receptor Agonists / Q000494:pharmacology*; D011725:Pyridines / Q000494:pharmacology; D011755:Pyrophosphatases / Q000037:antagonists & inhibitors; D011758:Pyrroles / Q000494:pharmacology; D058469:Receptors, Purinergic P2X / Q000502:physiology*; D013498:Suramin / Q000494:pharmacology; D014649:Vas Deferens / Q000502:physiology*; D054460:rho-Associated Kinases / Q000037:antagonists & inhibitors
C092431:6-N,N-diethyl-beta,gamma-dibromomethylene-D-ATP; D000577:Amides; D002120:Calcium Channel Agonists; D020746:Calcium Channels, L-Type; D051036:Large-Conductance Calcium-Activated Potassium Channels; D010455:Peptides; D026902:Potassium Channel Blockers; D024642:Potassium Channels, Voltage-Gated; D058911:Purinergic P2X Receptor Agonists; D011725:Pyridines; D011758:Pyrroles; D058469:Receptors, Purinergic P2X; C071658:FPL 64176; C108830:Y 27632; D001030:Apamin; D013498:Suramin; C064719:iberiotoxin; D000255:Adenosine Triphosphate; D015761:4-Aminopyridine; D054460:rho-Associated Kinases; D011755:Pyrophosphatases; C092064:ectonucleotide pyrophosphohydrolase; C002630:alpha,beta-methyleneadenosine 5'-triphosphate; D009638:Norepinephrine