Regulation of the substance P‐induced contraction via the release of acetylcholine and γ‐aminobutyric acid in the guinea‐pig urinary bladder

Shirakawa, Junji; Nakanishi, Tateo; Taniyama, Kohtaro; Kamidono, Sadao; Tanaka, Chikako

doi:10.1111/j.1476-5381.1989.tb12615.x

Cited by 16 publications

(13 citation statements)

References 23 publications

(29 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…More specific expression of GABA receptor subunits were identified in neuroendocrine cells including pancreatic ␤ (54, 59), pituitary (48), and adrenal cells (44). Indirect pharmacological evidence suggested GABA receptor expression in vascular (22), bladder (19), uterine (2,17,21), and gut (47) smooth muscle in addition to the identification of GABA receptors in the peripheral nerves that innervate these tissues (5,15,46,50). The expression of GABA receptors in these smooth muscles of gut, bladder, vascular, and uterine smooth muscle was inferred from pharmacological responses as opposed to a direct molecular identification of GABA receptors within the smooth muscle (2,17,19,21,22,39,47).…”

Section: Discussionmentioning

confidence: 96%

GABA_Areceptors are expressed and facilitate relaxation in airway smooth muscle

Mizuta¹,

Xu²,

Pan³

et al. 2008

American Journal of Physiology-Lung Cellular and Molecular Phys

View full text Add to dashboard Cite

Gamma-aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the mammalian central nervous system and exerts its actions via both ionotropic (GABA(A)) channels and metabotropic (GABA(B)) receptors. GABA(A) channels are ubiquitously expressed in neuronal tissues, and in mature neurons modulate an inward chloride current resulting in neuronal inhibition due to membrane hyperpolarization. In airway smooth muscle (ASM) cells, membrane hyperpolarization favors smooth muscle relaxation. Although GABA(A) channels and GABA(B) receptors have been functionally identified on peripheral nerves in the lung, GABA(A) channels have never been identified on ASM itself. We detected the mRNA encoding of the GABA(A) alpha(4)-, alpha(5)-, beta(3)-, delta-, gamma(1-3)-, pi-, and theta-subunits in total RNA isolated from native human and guinea pig ASM and from cultured human ASM cells. Selected immunoblots identified the GABA(A) alpha(4)-, alpha(5)-, beta(3)-, and gamma(2)-subunit proteins in native human and guinea pig ASM and cultured human ASM cells. The GABA(A) beta(3)-subunit protein was immunohistochemically localized to ASM in guinea pig tracheal rings. While muscimol, a specific GABA(A) channel agonist, did not affect the magnitude or the time to peak contractile effect of substance P, it directly concentration dependently relaxed a tachykinin-induced contraction in guinea pig tracheal rings, which was inhibited by the GABA(A)-selective antagonist gabazine. Muscimol also relaxed a contraction induced by an alternative contractile agonist histamine. These results demonstrate that functional GABA(A) channels are expressed on ASM and suggest a novel therapeutic target for the relaxation of ASM in diseases such as asthma and chronic obstructive lung disease.

show abstract

Section: Discussionmentioning

confidence: 96%

GABA_Areceptors are expressed and facilitate relaxation in airway smooth muscle

Mizuta¹,

Xu²,

Pan³

et al. 2008

American Journal of Physiology-Lung Cellular and Molecular Phys

View full text Add to dashboard Cite

show abstract

“…3 H]ACh outflow The methods of incubation and superfusion were as described by Kusunoki et al (17) and Shirakawa et al (18). The strips of urinary bladder were incubated at 37°C for 60 min with […”

Section: Measurement Of [mentioning

confidence: 99%

5-Hydroxytryptamine Receptors, Especially the 5-HT4 Receptor, in Guinea Pig Urinary Bladder

et al. 2002

Self Cite

View full text Add to dashboard Cite

ABSTRACT-The function of 5-hydroxytryptamine (5-HT) receptors, especially the 5-HT4 receptor, in the urinary bladder were examined in preparations isolated from the guinea pig by in vitro receptor autoradiography and determinations of mechanical activity and acetylcholine (ACh) release. Specific The bladder functions are controlled by the integration of excitatory, inhibitory and sensory nerve activity in the spinal cord, pons and forebrain; and 5-hydroxytryptamine (5-HT) has been identified as an inhibitory neurotransmitter in the micturition reflex pathway at spinal and supraspinal sites (1). In vivo studies have shown that the 5-HT1A receptor of some 5-HT receptor subtypes are important in the micturition reflex pathway (2 -4), especially at the spinal site (4). In vitro study has shown that 5-HT causes contractions of urinary bladder preparations from several mammals (5). In most species, activation of 5-HT 2 receptor has been reported to cause contractions due to direct stimulation of smooth muscle cells of cat (6, 7) and human (8) urinary bladder. Activation of 5-HT 3 receptor causes neurogenic contractions mediated by stimulation of the receptor located on the excitatory neurons in the cat (7), mouse (9), guinea pig (10), rabbit (11, 12), and human (13, 14). The 5-HT4 receptor has been suggested to be located on the excitatory neurons of urinary bladder and its activation facilitates cholinergic transmission in humans (14,15), while in the monkey urinary bladder, the 5-HT4 receptor is located post-junctionally and its activation causes inhibition of neurogenic contractions (16). In the guinea pig urinary bladder, it has been reported by mechanical experiments that 5-HT2A and 5-HT4 receptors are involved in enhancing purinergic transmission and the 5-HT 3 receptor is involved in enhancing cholinergic transmission (10).In order to elucidate the function of 5-HT receptor subtypes, especially 5-HT4 receptor in the urinary bladder, and interaction between localization and function of 5-HT 4 receptor, we examined effects of 5-HT and 5-HT antagonists on the responses to 5-HT using mechanical activity, acetylcholine (ACh) release and in vitro receptor autoradiography.

show abstract

“…Thus, it is apparent that SP has multiple sites of action, including the smooth muscle as well as pre-and postganglionic nerves. These conclusions are supported by direct examination of the effects of SP on neurons in the pelvic ganglion, where it has a direct excitatory action [101], and in isolated smooth-muscle strips, where SP evokes the release of acetylcholine from postganglionic nerve terminals [182]. However, in view of the antagonism of the action of SP by cholinoceptor antagonists, the observation that (D-Pro 2, D-Trp 7, 9)-SP reduces the neurogenic responses should not be taken as evidence that SP is a neuromuscular transmitter in this organ.…”

Section: Substance Pmentioning

confidence: 52%

“…Noradrenaline inhibits GABA release [181,182] and substance P can evoke GABA release [182]. In addition, the release of CGRP from sensory neurons can be enhanced or inhibited by activation of GABA A-or GABAB-receptors, respectively [178].…”

Section: Somatostatinmentioning

confidence: 99%

Non-adrenergic, non-cholinergic control of the urinary bladder

Hoyle

1994

World J Urol

View full text Add to dashboard Cite

In the urinary, bladder, ATP is an excitatory neuromuscular transmitter, possibly a cotransmitter with acetylcholine from postganglionic parasympathetic nerves, which activates P2X-purinoceptors. The synthesis of prostaglandins is closely linked to the activation of P2X-purinoceptors, and these compounds make a significant contribution to non-cholinergic neurogenic responses. Many neuropeptides, such as NPY, VIP, somatostatin, SP and CGRP, are found in nerves innervating the lower urinary tract, but it is unlikely that any is a neuromuscular transmitter in the detrusor; rather, they may act as potent modulators of sympathetic and parasympathetic transmission. Modulatory actions are shown by GABA par excellence; this compound is also well represented in vesicular neurons and, via activation of GABAA- or GABAB-receptors, can potentiate or inhibit parasympathetic transmission. Although not discussed in depth in this review, the urinary bladder shows extraordinary plasticity in expression of nerves and of their transmitters and receptors under pathophysiological conditions, including pregnancy and ageing as well as disease states. Finally, the accessibility of the urinary bladder and the enormous range of chemoreceptors that it possesses has led to its being used extensively for pharmacological investigations of transmitter and drug receptors and their subclasses.

show abstract

Regulation of the substance P‐induced contraction via the release of acetylcholine and γ‐aminobutyric acid in the guinea‐pig urinary bladder

Cited by 16 publications

References 23 publications

GABA_Areceptors are expressed and facilitate relaxation in airway smooth muscle

GABA_Areceptors are expressed and facilitate relaxation in airway smooth muscle

5-Hydroxytryptamine Receptors, Especially the 5-HT4 Receptor, in Guinea Pig Urinary Bladder

Non-adrenergic, non-cholinergic control of the urinary bladder

Contact Info

Product

Resources

About

Regulation of the substance P‐induced contraction via the release of acetylcholine and γ‐aminobutyric acid in the guinea‐pig urinary bladder

Cited by 16 publications

References 23 publications

GABAAreceptors are expressed and facilitate relaxation in airway smooth muscle

GABAAreceptors are expressed and facilitate relaxation in airway smooth muscle

5-Hydroxytryptamine Receptors, Especially the 5-HT4 Receptor, in Guinea Pig Urinary Bladder

Non-adrenergic, non-cholinergic control of the urinary bladder

Contact Info

Product

Resources

About

GABA_Areceptors are expressed and facilitate relaxation in airway smooth muscle

GABA_Areceptors are expressed and facilitate relaxation in airway smooth muscle