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Biomedical subjects

R Uddman

Publications and source records attributed to R Uddman.

At least 55 records · Page 3Linked to original sources
PubMed1996

A comparison of morphological effects on the rabbit nasal and sinus mucosa after surgical denervation and topical capsaicin application.

In order to study morphological effects on the nasal and sinus mucosa, New Zealand White rabbits underwent either unselective, regional sectioning of sensory and parasympathetic nerve branches or topical treatment of the mucosa with capsaicin. Ten days after treatment, mucosal specimens were analyzed by light and electron microscopy. Immunohistochemistry was used to evaluate neuropeptides present, in particular substance P, calcitonin gene-related peptide, vasoactive intestinal peptide and neuropeptide Y. In surgically denervated rabbits, mucosal glands were found to be enlarged and contained an increased number of zymogen granules having a bipartite substructure. Topical capsaicin application caused localized epithelial changes in the sinus mucosa and maxilloturbinal region of the nose, including clotting of cilia and an increased number of goblet cells. Reduced amounts of all neuropeptides investigated were found in the surgically denervated animals, while topical capsaicin treatment had only marginal effects on the mucosal neuropeptide content. The morphological changes observed after surgical denervation suggest an imbalance between neural stimulation and secretory capacity of the mucosal glands. These findings could explain the difference in clinical effect noted between sectioning of the vidian nerve and topical treatment with capsaicin in patients with perennial rhinitis.

Administration, Topical↗
PubMed1996

Pituitary adenylate cyclase-activating peptide-immunoreactive nerve fibers in the cat eye.

PURPOSE: To study the occurrence and distribution of the neuropeptide pituitary adenylate cyclase-activating peptide (PACAP) in ocular and orbital structures of the cat. METHODS: Immunocyto-chemistry to localize PACAP and double immunostaining to detect co-localization of PACAP with other neuropeptides. RESULTS: Numerous PACAP-immunoreactive nerve fibers were observed in the lacrimal gland, choroid and retroocular arteries. There was a sparse supply of PACAP-containing nerve fibers in the iris, ciliary body and conjunctiva. Subpopulations of PACAP-containing nerve fibers stored vasoactive intestinal peptide (VIP) or calcitonin gene-related peptide (CGRP). Around 10% of the ganglion cells in the sphenopalatine ganglion harbored PACAP immunoreactivity. In the trigeminal ganglion around 5% of the neuronal cell bodies and in the ciliary ganglion only occasional ganglion cells contained PACAP immunoreactivity. PACAP immunoreactivity co-localized with VIP in the sphenopalatine ganglion and with CGRP in the trigeminal ganglion. CONCLUSION: PACAP-containing nerves in the eye and associated structures demonstrate a distribution pattern resembling that of VIP. Subpopulations of nerve fibers containing PACAP immunoreactivity store VIP or CGRP immunoreactivity. Neuronal PACAP in the eye and orbit may take part in regulation of smooth muscle tone, glandular secretion and sensory processing.

Animals↗
PubMed1996

Vasoactive intestinal peptide- and nitric oxide synthase-containing nerve fibers in the rat ophthalmic artery have different origins.

BACKGROUND: Neuropeptides are important in the regulation of vascular functions. The purpose of the present study was to investigate the distribution of perivascular nerve fibers containing neuropeptides and nitric oxide synthase (NOS) in the rat ophthalmic artery. METHODS: Neuropeptide- and NOS-containing nerve fibers in the rat ophthalmic artery were identified using immunocytochemistry following unilateral parasympathectomy (electrocoagulation of the sphenopalatine ganglion) and sympathectomy (superior cervical ganglionectomy). The contralateral artery was used as control. RESULTS: Nerve fibers containing vasoactive intestinal peptide (VIP), neuropeptide Y (NPY) and NOS were abundant in the wall of the ophthalmic artery. Nerve fibers containing calcitonin gene-related peptide and substance P were scarcer. Following destruction of the sphenopalatine ganglion there was no discernible change in the density of VIP- and NPY-immunoreactive fibers, while the majority of the NOS-containing fibers disappeared. Following sympathectomy the NPY-containing nerve fibers were almost completely eliminated, whereas VIP- and NOS-containing fibers were unaffected. CONCLUSION: The present study demonstrates that the sphenopalatine ganglion is the main contributor of NOS-containing nerve fibers to the rat ophthalmic artery. In contrast, this ganglion apparently is of little importance as a source of VIP-immunoreactive nerve fibers to the artery, demonstrating different origins of the majority of the VIP-and NOS-containing fibers to this artery. The NPY-containing nerve fibers in the rat ophthalmic artery emanate mainly from the superior cervical ganglion.

Animals↗
PubMed1995

Pituitary adenylate cyclase activating polypeptide is expressed in autonomic neurons.

Pituitary adenylate cyclase activating polypeptide (PACAP) is a novel vasoactive intestinal peptide (VIP)-like peptide, which is present in neuronal elements of several peripheral organs, and thus a putative neurotransmitter/modulator. In the present study, the expression of PACAP in two parasympathetic ganglia (otic, sphenopalatine) and one mixed parasympathetic/sensory ganglion (jugular-nodose) in rat was characterized by use of in situ hybridization and immunocytochemistry and compared to that of VIP and calcitonin gene-related peptide (CGRP). PACAP and VIP were expressed in virtually all nerve cell bodies in the otic and sphenopalatine ganglia; PACAP and VIP were also expressed in subpopulations of nerve cell bodies in the jugular-nodose ganglion. CGRP was expressed in numerous nerve cell bodies in the jugular-nodose ganglion and in a few, scattered, nerve cell bodies in the sphenopalatine ganglion. In the otic and sphenopalatine ganglia, PACAP- and VIP-like immunoreactivities were frequently co-localized; in the jugular-nodose ganglion, PACAP-like immunoreactivity was frequently co-localized with CGRP-like immunoreactivity in presumably sensory neurons and to a lesser extent with VIP in parasympathetic neurons. Thus, PACAP is synthesized and stored in autonomic parasympathetic neurons as well as in vagal sensory neurons, which provides an anatomical basis for the diverse effects of PACAP previously described.

Animals↗
PubMed1995

Distribution and origin of the peripheral innervation of rat cervical esophagus.

Several neurotransmitters, neuropeptide Y (NPY), vasoactive intestinal peptide (VIP), galanin, enkephalin, calcitonin-gene related peptide (GGRP), substance P, as well as nitric oxide synthase (NOS), and the noradrenergic marker tyrosine-hydroxylase (TH) were localized by immunocytochemistry in the cervical esophagus of rat. Nerve fibers containing the neuropeptides, NOS, and TH were distributed in the myenteric plexus, around muscle bundles and small blood vessels. Injection of the retrograde tracer True Blue (TB) into the cervical esophagus resulted in the appearance of labeled nerve cell bodies in the superior cervical, the stellate, the nodose, the sphenopalatine, the dorsal root ganglia at levels C2-C7, and in local ganglia close to the thyroid. Most of the TB-labeled nerve cell bodies in the superior cervical ganglia contained NPY. In the stellate ganglion, a few labeled nerve cell bodies contained VIP whereas an additional few cell bodies stored VIP. In local ganglia, the majority of labeled cell bodies contained VIP. In the nodose ganglion and cervical dorsal root ganglia, the majority of the labeled nerve cell bodies stored CGRP. The results indicate that the cervical esophagus has a dense innervation with multiple neurotransmitters emanating from several ganglia. As judged by the pattern of nerve fiber distribution, they may regulate esophageal peristalsis and blood flow, some of them possibly in a cooperative manner.

Amino Acid Oxidoreductases↗
PubMed1995

Modification of vasoconstrictor responses in cerebral blood vessels by lesioning of the trigeminal nerve: possible involvement of CGRP.

The functional role of the trigeminal system has been addressed in experiments on the cortical surface of alpha-chloralose anaesthetized cats. Application of calcitonin gene-related peptide (CGRP) caused a concentration-dependent increase in arteriolar calibre by 38 +/- 5% (n = 8) with an IC50 of 2 nM. Cerebral veins did not relax upon CGRP administration (n = 12). Substance P (SP) was less potent but showed dilatation of both arterioles (21 +/- 4%) and veins (16 +/- 4%). The cerebrovascular trigeminal system was investigated after chronic (14 days) surgical lesion of the trigeminal nerve with the concomitant disappearance of perivascular CGRP/SP immunoreactive nerves. The cortical arteriolar responses to subarachnoid microinjections of acidic (pH 6.8) and basic CSF (pH 7.6) as well as noradrenaline (10(-4) M), neuropeptide Y (10(-7) M), prostaglandin F2x (10(-6 M), barium chloride (10(-4) M), and autologous blood (5 microl) were examined in anaesthetized cats with lesions of the trigeminal nerve, and were compared with their effects in sham-operated animals. The magnitude of the vasodilator and vasoconstrictor responses to these agents was unaffected by trigeminal lesions. However, duration of the vasoconstriction produced by basic CSF, but not the vasodilitation to acidic CSF, was markedly prolonged by trigeminal lesions (from 0.8 +/- 0.1 min to 2.2 +/- 0.3 min, p < 0.01). Also, the vasoconstrictor responses to noradrenaline, prostaglandin F2x, barium chloride, and autologous blood were significantly prolonged, while the maximum contractile effect to each agent was similar in lesioned as in sham-operated controls. The effects of CGRP, SP, and neurokinin A (NKA) have been examined on isolated cerebral arteries in vitro. Different CGRP analogues induced a strong relaxation with no difference in Imax (85-96%) or pD2 values (8.65 - 9.12). NKA induced a stronger relaxation than SP (Imax: 33% and 13%, respectively). SP was more potent than NKA (pD2:8.7 and 7.7, respectively). Capsaicin, a substance which selectively causes the release of stored sensory neuropeptides (CGRP, SP, NKA), caused in vitro relaxation of precontracted arteries. This relaxation was not affected by the neurokinin blocker spantide, but shifted towards higher capsaicin concentrations by the CGRP antagonist (CGRP 8-37. Thus, in this preparation CGRP rather than a neurokinin (SP/NKA) is responsible for the capsaicin-induced dilatations.

Animals↗
PubMed1995

Neuropeptide Y (NPY) in the orbital arteries of the rabbit. Immunocytochemistry and vasomotor activity.

The purpose of the present study was to investigate the presence and vascular effects of neuropeptide Y in the rabbit orbital arteries. Neuropeptide Y-containing nerve fibers were demonstrated, using an indirect immunofluorescence method with a neuropeptide Y antiserum raised in goat against porcine neuropeptide Y. Isometric responses in isolated circular segments of the orbital arteries were measured following application of neuropeptide Y, different contracting agonists, and the neuropeptide Y blocker alpha-trinositol. A rich supply of neuropeptide Y-containing nerve fibers was seen around the orbital arteries. Neuropeptide Y (10(-10)-10(-6) M) did not induce any contractions in resting arterial segments. Noradrenaline and histamine evoked concentration dependent constrictions which were potentiated by neuropeptide Y (3 x 10(-7) M). This potentiation was completely blocked by alpha-trinositol (3 x 10(7) M). The contractile effects of endothelin-1, endothelin-3, prostaglandin F2 alpha, and 5-hydroxytryptamine were not modified by neuropeptide Y.

Animals↗
PubMed1995

Islet amyloid polypeptide (amylin) is expressed in sensory neurons.

Islet amyloid polypeptide (IAPP) or amylin is a hormone candidate predominantly expressed in insulin cells. A role for IAPP in the regulation of glucose homeostasis and the development of non-insulin-dependent diabetes mellitus has been proposed. IAPP is structurally related to the sensory neuropeptide calcitonin gene-related peptide. In the present study, using in situ hybridization, immunocytochemistry, and immunochemistry, the expression of IAPP in sensory neurons in the rat was investigated. IAPP was expressed in a population of small- to medium-sized nerve cell bodies in dorsal root ganglia from all levels and in the jugular-nodose and trigeminal ganglion; IAPP-expressing nerve cell bodies constituted a subpopulation of those expressing calcitonin gene-related peptide. In addition, IAPP-like immunoreactivity occurred in nerve cell bodies storing substance P and pituitary adenylate cyclase-activating polypeptide. IAPP-immunoreactive nerve fibers were encountered in the dorsal horns of the spinal cord, and to a lesser extent in peripheral tissues receiving sensory innervation; IAPP-immunoreactive fibers constituted a subpopulation of those containing calcitonin gene-related peptide and/or substance P. The immunochemical determinations demonstrated a low level of IAPP-like immunoreactivity in the dorsal root ganglia and spinal cord, which chromatographically coeluted with authentic rat IAPP. We conclude that IAPP is expressed in sensory neurons, thus being a novel sensory neuropeptide candidate for which a physiological role remains to be identified.

Amyloid↗
PubMed1994

Calcitonin, CGRP and helodermin in endocrine cells of the developing rat lung.

Calcitonin gene-related peptide (CGRP), calcitonin and immunoreactive helodermin occur in endocrine cells in the murine airways. In the lungs these cells form clusters, while they occur scattered in the larynx and trachea. In the present study of the developing rat CGRP-immunoreactive cells were more numerous at all stages than the calcitonin- and helodermin-containing ones. A subpopulation of the CGRP-containing cells contained either calcitonin or helodermin. Immunocytochemistry revealed a higher density of CGRP-containing endocrine cells in the lungs of fetal and newborn rats than in the lungs of older rats, while the density of calcitonin-containing cells was largely unchanged. The helodermin-containing cells were few at all developmental stages examined. The concentration and content of CGRP were highest in newborn rats; the levels decreased postnatally. The calcitonin concentration did not change during development while the content increased with age. The concentration and content of helodermin increased with age.

Aging↗
PubMed1994

Neuronal pathways to the rat conjunctiva revealed by retrograde tracing and immunocytochemistry.

The origin and neuropeptide content of nerve fibres in the rat conjunctiva were studied by retrograde tracing and denervations in combination with immunocytochemistry. Immunocytochemistry revealed nerve fibres containing neuropeptide Y (NPY), vasoactive intestinal peptide (VIP), peptide histidine isoleucine (PHI), helospectin, substance P (SP), and calcitonin gene-related peptide (CGRP) around blood vessels, smooth muscle bundles and glands. Removal of the sphenopalatine ganglion eliminated the majority of the VIP-, PHI- and helospectin-containing fibres. Sympathectomy eliminated the majority of the NPY-containing fibres in the conjunctiva. Removal of both the sphenopalatine ganglion and the superior cervical ganglion led to further reduction of the NPY fibres. Injection of the retrograde tracer True Blue into the conjunctiva resulted in the appearance of labelled cell bodies in the trigeminal ganglion, the sphenopalatine ganglion, the superior cervical ganglion, and the ciliary ganglion. Judging from the number of labelled nerve cell bodies, the superior cervical ganglion contributes most to the innervation. These results indicate that the majority of NPY-containing nerve fibres in the conjunctiva derives from the superior cervical ganglion (sympathetic nerve supply). Most of the VIP- and a minor population of the NPY-containing fibres in the conjunctiva originate in the sphenopalatine ganglion (parasympathetic nerve supply). A sparse amount of VIP- and NPY-containing fibres derives from the ciliary ganglion. Nerve fibres containing SP and/or CGRP emanate from the trigeminal ganglia (sensory nerve supply). Together the findings indicate that several ganglia project to the conjunctiva and that many neuropeptides may be involved in the control of conjunctival activity.

Animals↗
PubMed1994

Origin and peptide content of nerve fibers in the nasal mucosa of rats.

Injection of the retrograde neuronal tracer True blue into the anterior-lateral part of the nasal mucosa of rats labeled nerve cell bodies in the superior cervical ganglion, the sphenopalatine ganglion, the otic ganglion and the trigeminal ganglion on the ipsilateral side. In the superior cervical ganglion, the sphenopalatine ganglion and the trigeminal ganglion on the contralateral side, very few nerve cell bodies were labeled, indicating that these ganglia provide minor contributions only. The number of labeled cell bodies indicates that the superior cervical ganglion, the sphenopalatine ganglion and the trigeminal ganglion contribute most to the innervation of the nose, while the contribution from the otic ganglion is minor. Cell bodies in the superior cervical ganglion harbored noradrenaline (NA) or NA/neuropeptide Y (NPY); in the sphenopalatine ganglion vasoactive intestinal peptide (VIP) or VIP/NPY; in the otic ganglion VIP, VIP/NPY or VIP/substance P (SP) and in the trigeminal ganglion calcitonin gene-related peptide (CGRP) or CGRP/SP. The results from denervations and tracer experiments suggest that all NA-containing and the majority of NPY-containing fibers in the nasal mucosa are derived from the superior cervical ganglion (sympathetic nerve supply). VIP- and VIP/NPY-containing fibers originate from the sphenopalatine and optic ganglia (parasympathetic nerve supply). Nerve fibers containing CGRP and CGRP/SP emanate from the trigeminal ganglion (sensory nerve supply).

Animals↗
PubMed1994

NOS-containing neurons in the rat gut and coeliac ganglia.

Nitric oxide (NO) is considered an important inhibitory neurotransmitter in the gut. Nitric oxide synthase (NOS)-containing neurons were visualized by immunocytochemistry using antibodies against neuronal NOS in the oesophagus, the gastrointestinal tract and the coeliac ganglion of rat. NOS-containing nerve cell bodies were numerous in the myenteric but fewer in the submucous ganglia all along the gut. Synthesis of NOS in enteric nerve cell bodies was confirmed by in situ hybridization, demonstrating the presence of NOS mRNA. Varicose nerve fibers formed extensive networks in the circular smooth muscle and the myenteric ganglia. The pyloric sphincter contained abundant NOS-containing nerve fibers. NOS-containing nerve terminals were frequently found around the Brunner glands in the duodenum; scattered nerve terminals occurred in the gastric and colonic mucosa and around blood vessels in the submucosa all along the gut. The neuronal cell bodies in the coeliac ganglion were non-immunoreactive but frequently surrounded by baskets of NOS-immunoreactive nerve fibers. Double staining for NOS and neuropeptides in oesophagus, stomach and small and large intestine revealed that a small subpopulation of the NOS-containing nerve cell bodies stored in addition vasoactive intestinal peptide (VIP), and in oesophagus, stomach and small intestine also neuropeptide Y (NPY). However, NOS-containing nerve terminals, particularly those in the circular muscle of the gut, frequently contained VIP throughout the gut; in the oesophagus, stomach and the small intestine they contained also NPY.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Oxidoreductases↗
PubMed1994

Vasoactive intestinal peptide (VIP) like peptides in the cerebral circulation of the cat.

The present study was designed to study the localization and effects of some VIP-related peptides on the cerebral circulation in cats. A rich supply of nerve fibres containing vasoactive intestinal peptide- (VIP) was seen. Nerve fibres containing pituitary adenylate cyclase activating peptide and helospectin-like immunoreactivity (-IR) were moderate in numbers whereas only a sparse supply of fibres containing helodermin-IR was seen. Double immunostaining revealed that the majority of PACAP- and helospectin-IR nerve fibres contained VIP. Using a sensitive in vitro system prostaglandin F2 alpha-precontracted circular segments of the cat middle cerebral artery relaxed upon administration of VIP, PACAP, helospectin I, helospectin II and helodermin. These effects were non-endothelium dependent with pD2-values varying between 7.6 and 8.1. The maximum relaxation varied between 47% and 79% of precontraction. Local cerebral blood flow was studied in anaesthetised cats. Cortical injection of PACAP-38, helospectin or helodermin, 5 micrograms in a volume of 1 microliter, revealed moderate and consistent increases in flow. The increase in cerebral blood flow was rapid and concentration-dependent with maximum increases of 18 +/- 6% for PACAP, 21 +/- 5% for helodermin, 16 +/- 7% for helospectin I and 19 +/- 5% for helospectin II. The vehicle caused no significant response (2 +/- 4%).

Animals↗
PubMed1994

Pituitary adenylate cyclase activating polypeptide expression in sensory neurons.

Pituitary adenylate cyclase activating polypeptide (PACAP) is a novel vasoactive intestinal peptide (VIP)-like peptide isolated from ovine hypothalami. The presence of PACAP-like immunoreactivity was recently demonstrated in nerve cell bodies of sensory ganglia in the rat. Since PACAP belongs to a large family of chemically related neuropeptides, we have, in the present study, tried to establish the synthesis of PACAP in neurons of sensory ganglia, using in situ hybridization with a 35S-labelled oligonucleotide probe complementary to PACAP mRNA. The expression of PACAP was compared to that of calcitonin gene-related peptide (CGRP) using a radiolabelled CGRP oligonucleotide probe. The PACAP probe labelled small to medium-sized neurons in the trigeminal ganglion and dorsal root ganglia at different levels, indicating the presence of PACAP mRNA. The CGRP probe labelled nerve cell bodies of varying size, outnumbering those labelled by the PACAP probe. In dorsal root ganglia, cells expressing PACAP constituted c. 10% and those expressing CGRP 46% of the total number of nerve cell bodies. Expression of PACAP was seen in a small subpopulation of cells expressing CGRP. We conclude that PACAP is synthesized in a subpopulation of neurons of sensory ganglia in the rat. Therefore, the recently described effects of PACAP--cutaneous vasodilation, potentiation of oedema formation and depression of nociceptive spinal reflexes--may be physiological and related to neurogenic inflammation and modulation of pain transmission.

Animals↗
PubMed1994

Endothelins: a role in cerebrovascular disease?

Vasoactive factors produced and released by the endothelium exert a powerful influence on vascular tone in the cerebral circulation. Impaired endothelium-dependent responses, such as decreased production of endothelium-derived relaxing factors, and/or release of endothelium-derived contractile factors may give rise to different pathophysiological conditions. Among the endothelium-derived contractile factors the endothelins have recently received particular attention. Endothelin-1 is the major isoform in the endothelin family, which also includes endothelin-2 and endothelin-3. Endothelin-1 is synthesized within the endothelium of cerebral vessels, whereas both endothelin-1 and endothelin-3 in addition have been identified in neurons and glia. Recent electrophysiological work has suggested a neuromodulatory role for these peptides, but at present the general interest is mainly focused on their vasoactive role. Physiological stimuli such as hypoxia, anoxia, and hemodynamic shear stress will stimulate the endothelial endothelin production. In the brain, at least two types of specific subreceptors have been cloned; ETA receptors, exclusively associated with blood vessels and ETB receptors also found on glial, epithelial, and ependymal cells. The endothelins seem so far to be the most potent vasoconstrictors yet identified. The circulating plasma levels of immunoreactive endothelin are low. Since more than 80% of the total amount released from endothelial cells seems to be secreted towards the underlying smooth muscle, endothelins have been ascribed a local vasoregulatory role. Endothelins are believed to be involved in several of our most common cerebrovascular diseases and the present review comments on their possible pathophysiological role in subarachnoid haemorrhage, cerebral ischemia, and migraine.

Amino Acid Sequence↗
PubMed1994

Low plasma concentrations of VIP and elevated levels of other neuropeptides during exacerbations of asthma.

Neuropeptides in the lung occur in neurons, neuroendocrine and inflammatory cells. Their widespread distribution and physiological effects suggest that they may play important roles in asthma. We investigated whether, during an exacerbation of asthma, patients displayed changes in plasma levels of the neuropeptides vasoactive intestinal peptide (VIP), calcitonin gene-related peptide (CGRP), substance P (SP), and neuropeptide Y (NPY). Venous blood from 25 adult patients attending the emergency ward with an exacerbation of asthma was sampled before and after treatment. Plasma levels of VIP-, SP-, CGRP- and NPY-like immunoreactivity (-LI) were determined by immunoassay, and the results obtained were compared with findings in 21 healthy controls. The mean plasma levels of VIP-LI were lower in patients (3.4 +/- 0.4 pmol.l-1) than in controls (10.4 +/- 0.7 pmol.l-1), whereas the levels of CGRP-LI (43.7 +/- 3.4 pmol.l-1), SP-LI (4.6 +/- 0.4 pmol.l-1) and NPY-LI levels (159 +/- 6 pmol.l-1) were higher in patients than in controls (21.1 +/- 3.4; 2.2 +/- 0.2 and 105 +/- 8 pmol.l-1, respectively). A relationship was seen between the reversibility of obstruction, expressed as improvement of peak expiratory flow upon treatment, and the neuropeptide levels, such that lower VIP-LI levels and higher CGRP-LI levels correlated with less reversibility. Plasma levels of neuropeptides, VIP-LI and CGRP-LI in particular, may therefore be employed as predictors of responsiveness to bronchodilatory therapy.

Acute Disease↗
PubMed1993

Helospectin/helodermin-like peptides in guinea pig lung: distribution and dilatory effects.

The lower airways of guinea pigs were analysed for helospectin and helodermin using immunocytochemistry. A moderate supply of helospectin/helodermin-like immunoreactive nerve fibers and few nerve fibers displaying helodermin immunoreactivity was seen in the smooth muscle, around seromucous glands and small blood vessels in the trachea and around bronchi and pulmonary blood vessels. Helospectin I-, helospectin II- and helodermin-induced suppression of smooth muscle responses were analysed using isolated circular segments of trachea and pulmonary arteries of guinea pigs. In both airways and arteries the peptides caused a concentration-dependent relaxation of precontracted segments. The maximal relaxant activity observed was more pronounced in the airways than in the arteries. The effects of the helospectins and helodermin were compared to those of vasoactive intestinal peptide (VIP), peptide histidine isoleucine (PHI), pituitary adenylate cyclase activating peptide (PACAP) and acetylcholine (ACh). All peptides, with the exception of PACAP, caused a total or nearly total relaxation of the precontracted tracheal segments. In the trachea PACAP was significantly more potent than the other five peptides whereas only small potency differences were seen in the pulmonary artery. The relaxant responses to helospectin I, helospectin II and helodermin in the trachea and the intrapulmonary arteries were unaffected by pretreatment with atropine, prazosin, yohimbine, propranolol, mepyramine and cimetidine. Conceivably, nerve fibers containing helospectin and helodermin may play a role in the regulation of airway resistance and in the regulation of local pulmonary blood flow.

Acetylcholine↗