Neural mechanisms underlying migrating motor complex formation in mouse isolated colon.

1. Little is known about the intrinsic enteric reflex pathways associated with migrating motor complex (MMC) formation. Acetylcholine (ACh) mediates the rapid component of the MMC, however a non-cholinergic component also exists. The present study investigated the possible role of endogenous tachykinins (TKs) in the formation of colonic MMCs and the relative roles of excitatory and inhibitory pathways. 2. MMCs were recorded from the circular muscle at four sites (proximal, proximal-mid, mid-distal and distal) along the mouse colon using force transducers. 3. The tachykinin (NK(1) and NK(2)) receptor antagonists SR-140 333 (250 nM) and SR-48 968 (250 nM) reduced the amplitude of MMCs at all recording sites, preferentially abolishing the long duration contraction. Residual MMCs were abolished by the subsequent addition of atropine (1 microM). 4. The neuronal nitric oxide synthase inhibitor, N(omega)nitro-L-arginine (L-NOARG, 100 microM), increased MMC amplitude in the distal region, whilst reducing the amplitude in the proximal region. In preparations where MMCs did not migrate to the distal colon, addition of L-NOARG resulted in the formation of MMCs. Subsequent addition of apamin (250 nM) or suramin (100 microM) further increased MMC amplitude in the distal region, whilst suramin increased MMC amplitude in the mid-distal region. Apamin but not suramin reduced MMC amplitude in the proximal region. Subsequent addition of SR-140 333 and SR-48 968 reduced MMC amplitude at all sites. Residual MMCs were abolished by atropine (1 microM). 5. In conclusion, TKs, ACh, nitric oxide (NO) and ATP are involved in the neural mechanisms underlying the formation of MMCs in the mouse colon. Tachykinins mediate the long duration component of the MMC via NK(1) and NK(2) receptors. Inhibitory pathways may be involved in determining whether MMCs are formed.

Heterogeneity of vascular innervation in hamster cheek pouch and retractor muscle.

The hamster cheek pouch and its retractor muscle have provided valuable insights into microvascular physiology of an epithelial tissue and striated muscle, respectively. Nevertheless, the innervation of these vascular beds has not been resolved. This study has investigated the nature of autonomic and sensory innervation of these vascular beds and has tested whether it varies within or between tissues. Multiple-labelling immunohistochemistry identified autonomic and peptide-containing sensory nerve fibres. Presumptive sympathetic vasoconstrictor axons with immunoreactivity (IR) for tyrosine hydroxylase (TH) and neuropeptide Y (NPY) innervated feed arteries and arterioles (but not veins or venules) of the retractor and anterior (muscular) cheek pouch; these axons were absent from the posterior (epithelial) region of the cheek pouch, as confirmed by catecholamine fluorescence. Presumptive autonomic vasodilator axons with IR for vasoactive intestinal peptide (VIP) consistently innervated feed arteries and proximal arterioles of the cheek pouch, but generally not those of the retractor muscle nor distal arterioles of either tissue. Sparse presumptive sensory axons with IR for calcitonin gene-related peptide (CGRP) and substance P were found near arterial and venous vessels in all regions of the cheek pouch and retractor muscle; CGRP-IR was also located in motor end plates associated with striated muscle fibres. Such regional differences in vascular innervation by autonomic and sensory neurons may selectively effect local and regional control of blood flow between and within vascular beds.

Neurochemical distinction between skeletal muscle vasodilator neurons and pelvic vasodilator neurons in guinea-pigs.

This study sets out to compare the combinations of potential vasodilator transmitters expressed by sympathetic and pelvic vasodilator neurons of guinea-pigs. Triple-labelling fluorescence immunohistochemistry was used to examine immunoreactivity (IR) to vasoactive intestinal peptide (VIP), nitric oxide synthase (NOS) and calcitonin gene-related peptide (CGRP) in lumbar sympathetic ganglia, and in perivascular axons supplying hindlimb skeletal muscles or pelvic viscera. Only 0.2% of VIP-IR nerve cell bodies in lumbar sympathetic ganglia (n = 4632 VIP-IR nerve cell profiles) contained NOS-IR, and one VIP-IR neuron contained CGRP-IR. The VIP-IR perivascular axons along the common and external iliac arteries, femoral artery and arteries to hindlimb muscles lacked NOS-IR and CGRP-IR. In contrast, all VIP-IR perivascular axons projecting from pelvic ganglia to the main uterine artery, and half of the VIP-IR axons along the internal iliac artery, contained NOS-IR and CGRP-IR. Thus, the neurochemical content of sympathetic vasodilator neurons to skeletal muscle arteries was clearly distinguishable from that of pelvic vasodilator neurons to the uterine vasculature. Furthermore, the autonomic dilation in each vascular bed is likely to be qualitatively different, and matched to the functional requirements of each target organ.

Projections of sympathetic non-noradrenergic neurons to skeletal muscle arteries in guinea-pig limbs vary with the metabolic character of muscles.

This study set out to examine in detail the distribution of axons of sympathetic non-noradrenergic neurons innervating the arterial bed in skeletal muscles of the forelimb and hindlimb of guinea-pigs. The distribution of non-noradrenergic axons with immunoreactivity to vasoactive intestinal peptide (VIP) was examined in limb muscles of different histochemical character. The immunohistochemical demonstration of myosin heavy chain from fast-twitch muscle, and the histochemical demonstration of adenosine triphosphatase and succinic dehydrogenase, were used to determine the muscle fibre profile of 6 different limb muscles. Muscles included the oxidative type I muscle fibre-rich accessory semimembranosus muscle, the predominantly glycolytic type II muscle fibre-rich cranial gracilis and biceps brachii muscles and the plantaris, gastrocnemius medial head and triceps brachii long head of mixed muscle fibre composition. The frequency with which the VIP-immunoreactive (VIP-IR) axons innervated intramuscular arterial vessels was compared between categories of muscles defined by their muscle fibre profile. This study demonstrated that the projection of non-noradrenergic sympathetic neurons to skeletal muscle vasculature was widespread in guinea-pig limb muscles, but that it was not uniform. VIP-IR axons were more likely to innervate the arterial vasculature of muscles with a high proportion of type I and/or oxidative muscle fibres than of muscles with a large proportion of type IIb muscle fibres. This relationship between the distribution of sympathetic non-noradrenergic axons and the metabolic characteristics of muscle suggests that these presumed vasodilator neurons have an important role in matching blood flow to the particular metabolic demands of different limb muscles.