Smooth muscle does not have a common P-2x receptor phenotype: expression, ontogeny and function of P-2x1 receptors in mouse ileum, bladder and reproductive systems

The distribution, ontogeny and rote of P-2x1 receptors were examined in the smooth muscle of the mouse intestine, bladder, and male and female reprodu ctive tracts using P-2x1 receptor subtype selective antibodies and contract ion studies. P-2x1 receptor immunoreactivity showed a heterogeneous distrib ution in smooth muscle with high levels expressed in adult vas deferens, bl adder, arteries and male reproductive organs. In contrast, P-2x1 receptors were below the level of detection in the smooth muscle of the ileum and fem ale reproductive tract. P-2x1 receptor immunoreactivity was detected at adu lt levels from birth in the bladder. However, in the vas deferens, immunore activity was only detected from 10 days after birth and reached adult level s by similar to1 month old. A similar pattern of expression was seen in the vesicular seminalis, epididymis, gland of the vas deferens and coagulating gland. Sensitivity to the P-2x1 receptor agonist alpha,beta -methylene ATP (alpha,beta -meATP) and P-2x1 receptor-deficient mice were used in functio nal studies to determine the role of P-2x1 receptors in the control of smoo th muscle. alpha,beta -meATP (100 muM) failed to evoke contractions of the epididymis, or seminal vesicle and P-2x1 receptors did not contribute to th e control of uterine smooth muscle. In the ileum, alpha,beta -meATP (100 mu M) evoked a transient relaxation followed by a contraction. These responses were abolished by the P-2 receptor antagonist iso-pyridoxalphosphate-6-azo phenyl-2'-5'-disulphonate (iso-PPADS) (30 muM). Relaxant responses were abo lished by the adenosine A(1) receptor antagonist 1,3-dipropyl-8-cyclopentyl xanthine (DPCPX) (1 muM). Contractile responses were reduced by > 80% in th e ileum from P-2x1 receptor-deficient mice. alpha,beta -meATP-evoked contra ctions were, reduced by similar to 35% by TTX (1 muM) and were unaffected b y atropine (10 muM). These studies indicate that P-2x1 receptors are not ex pressed throughout all smooth muscles and that their expression is developm entally regulated. In addition, they provide evidence to suggest that P-2x1 receptors are present on pre-synaptic nerve terminals in the enteric nervo us system. (C) 2001 Elsevier Science B.V. All rights reserved.