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Biomedical subjects

G Tobin

Publications and source records attributed to G Tobin.

At least 19 recordsLinked to original sources
PubMed2006

The G(-248)A polymorphism in the promoter region of the Bax gene does not correlate with prognostic markers or overall survival in chronic lymphocytic leukemia.

The G(-248)A polymorphism in the promoter region of the Bax gene was recently associated with low Bax expression, more advanced stage, treatment resistance and short overall survival in B-cell chronic lymphocytic leukemia (CLL), the latter particularly in treated patients. To investigate this further, we analyzed 463 CLL patients regarding the presence or absence of the G(-248)A polymorphism and correlated with overall survival, treatment status and known prognostic factors, for example, Binet stage, VH mutation status and genomic aberrations. In this material, similar allele and genotype frequencies of the Bax polymorphism were demonstrated in CLL patients and controls (n=207), where 19 and 21% carried this polymorphism, respectively, and no skewed distribution of the polymorphism was evident between different Binet stages and VH mutated and unmutated CLLs. Furthermore, no difference in overall survival was shown between patients displaying the G(-248)A polymorphism or not (median survival 85 and 102 months, respectively, P=0.21), and the polymorphism did not influence outcome specifically in treated CLL. Neither did the polymorphism affect outcome in prognostic subsets defined by VH mutation status or genomic aberrations. In conclusion, the pathogenic role and clinical impact of the Bax polymorphism is limited in CLL.

Adult↗
PubMed2005

Distribution and function of muscarinic receptor subtypes in the ovine submandibular gland.

The effects of muscarinic receptor antagonists on responses to electrical stimulation of the chorda-lingual nerve were determined in pentobarbitone-anesthetized sheep and correlated to the morphology of tissue specimens. Stimulation at 2 Hz continuously, or in bursts of 1 s at 20 Hz every 10 s, for 10 min induced similar submandibular fluid responses (19 +/- 3 vs. 21 +/- 3 microl x min(-1) x g gland(-1)), whereas vasodilatation was greater during stimulation in bursts (-52 +/- 4 vs. -43 +/- 5%; P < 0.01). Continuous stimulation at 8 Hz induced substantially greater responses (66 +/- 9 microl x min(-1) x g gland(-1) and -77 +/- 3%). While atropine (0.5 mg/kg iv) abolished the secretory response at 2 and 20 Hz (1:10 s), a small response persisted at 8 Hz (<5%). The "M1-selective" antagonist pirenzepine (40 microg/kg iv) reduced the fluid response at all frequencies tested (P < 0.05-0.01), most conspicuously at 2 Hz (reduced by 69%). Methoctramine ("M2/M4-selective"; 100 microg/kg iv; n = 5) had no effect on fluid or the vascular responses but increased the protein output at 2 (+90%, P < 0.05) and 8 Hz (+45%, P < 0.05). The immunoblotting showed distinct bands for muscarinic M1, M3, M4, and M5 receptors, and immunohistochemistry showed muscarinic M1 and M3 receptors to occur in the parenchyma. Thus muscarinic M1 receptors contribute to the secretory response to parasympathetic stimulation but have little effect on the vasodilatation in the ovine submandibular gland. Increased transmitter release caused by blockade of neuronal inhibitory receptors of the M4 subtype would explain the increase in protein output.

Animals↗
PubMed2005

Altered muscarinic receptor subtype expression and functional responses in cyclophosphamide induced cystitis in rats.

In the in vitro study, it was investigated whether the expression of muscarinic receptors and cholinergic responses were altered in the situation of experimental cystitis. Rats were treated with cyclophosphamide intraperitoneally and the bladders were excised 36-100 h later. Immunohistochemistry and immunoblotting showed all subtypes of the muscarinic receptor (M1-M5) to be present in the specimens from inflamed urinary bladders and controls. In the cyclophosphamide-treated rats, the expression of muscarinic M5 receptors was increased by more than 40 times (p<0.01; n=8) both in the smooth muscle and the urothelium. Both the maximal contractile response to carbachol and to a high potassium concentration was approximately halved in cyclophosphamide-treated tissues, whereas the reduction was substantially greater in response to low carbachol concentrations (<EC(50)). The administration of 4-DAMP inhibited the carbachol-induced contractile responses of inflamed strips less potently than of controls, whereas pirenzepine and methoctramine showed equipotency in the two groups. The nitric oxide synthase inhibitor l-NNA increased the contractile effect of carbachol in inflamed detrusor strips, while it had no effect in controls. Immunoblotting showed endothelial nitric oxide synthase (eNOS) to be up-regulated in cystitis, and immunohistochemistry revealed the change to occur in the urothelium and in the suburothelial layer. The alteration of cholinergic detrusor responses in cyclophosphamide-treated rats depends mainly on a general detriment of contractility but also on indirect effects possibly via nitric oxide synthesis. The most prominent histological alterations occurred in the urothelium in which muscarinic M5 receptors increased in particular. The study further underlines that the urothelium may play significant roles in the pathogenesis of urinary bladder disorders such as interstitial cystitis.

Animals↗
PubMed2005

Postjunctional modulation by muscarinic M2 receptors of responses to electrical field stimulation of rat detrusor muscle preparations.

1. The aim of the present study was to examine the modulator influence of muscarinic M(2) receptors on responses of rat urinary bladder detrusor muscle evoked by endogenous stimuli, i.e. by stimulation of the bladder innervation. 2. Responses were evoked by electrical field stimulation (EFS; 2-20 Hz, 0.8 ms, 60 V) of isolated strip preparations mounted in organ baths. The tension of the muscle strips was recorded digitally. EFS was performed by applying stimulation with either a short duration (5 s) or a longer duration (to reach peak response; approximately 20 s). 3. Effects of muscarinic receptor antagonists (muscarinic M(1)/M(3) receptor selective: 4-diphenylacetoxy-N-methylpiperidine methobromide (4-DAMP); muscarinic M(2) receptor selective: methoctramine), a beta-adrenergic antagonist (propranolol) and an adenosine receptor antagonist (8-p-sulfophenyltheophylline) were assessed on contractile activity and on poststimulatory relaxations. 4. Low concentrations of methoctramine (10(-8) m) reduced or tended to reduce the EFS-induced contraction, e.g. at 2 Hz by 12% while methoctramine at 10(-7) m had no significant effect. In addition, in the presence of 4-DAMP (10(-9) m), which tended to inhibit contractions at all frequencies (2-20 Hz; -17 to -25%), methoctramine at 10(-8) and 10(-7) m induced a further reduction of the contractile responses (-5 to -10%; 2-20 Hz). 5. The beta-adrenergic receptor antagonist propranolol (10(-6) m) and the adenosine receptor antagonist 8-p-sulfophenyltheophylline (10(-6) m) both increased contractile responses by 9-21% (2-10 Hz, long duration; P < 0.05-0.001) as a consequence of antagonizing relaxatory stimuli. Neither antagonist affected the contractile responses to EFS with the short duration stimulation. Poststimulatory relaxations were reduced by 30-60% (P < 0.05) by propranolol and by 40-60% (P < 0.001) by 8-p-sulfophenyltheophylline, but for 8-p-sulfophenyltheophylline only after stimulation with the short duration. 6. In the presence of methoctramine (10(-7) m), the 8-p-sulfophenyltheophylline-induced increases of the contractile response to long duration EFS were significantly enhanced at 10 Hz (+12 +/- 4%; P < 0.05), whereas no such enhancement of the propranolol inhibitory effect occurred in the presence of methoctramine. However, poststimulatory beta-adrenoceptor-evoked relaxations after short duration EFS were increased by about 35% in the presence of methoctramine, but not those after long duration. 7. Thus, muscarinic M(2) receptor activation inhibits adenosine receptor- and beta-adrenoceptor-evoked relaxations of the rat detrusor muscle. The inhibition occurs via a transient postjunctional mechanism that mainly affects responses with a short latency.

Animals↗
PubMed2004

Oral pilocarpine for treatment of opioid-induced oral dryness in healthy adults.

Pilocarpine induces a profuse flow of saliva when administered orally, but effects on drug-induced oral dryness have not been examined. The aim of this trial was to investigate if pilocarpine increases production of saliva in individuals suffering from dry mouth due to treatment with opioids. Sixty-five individuals were enrolled in a randomized, double-blind, placebo-controlled trial. The subjects received tramadol (50 mg t.d.s.) to induce oral dryness, and were thereafter assigned to one of three groups. Secretion rate of saliva was measured before and after tramadol, and after the oral administration of pilocarpine (5 mg), placebo, or no treatment. Baseline characteristics did not differ among the groups (mean +/- SEM: 0.37 +/- 0.06 mL/min), and tramadol lowered the secretion at the same level in all groups (0.15 +/- 0.02 mL/min). Pilocarpine increased the flow above that observed with placebo (0.66 +/- 0.19 vs. 0.15 +/- 0.02 mL/min). Thus, pilocarpine re-establishes the flow of saliva in the state of tramadol-induced oral dryness.

Administration, Oral↗
PubMed2003

Association between telomere length and V(H) gene mutation status in chronic lymphocytic leukaemia: clinical and biological implications.

The immunoglobulin V(H) gene mutation status can divide B-cell chronic lymphocytic leukaemia (CLL) into two entities with a different clinical course. Cases with unmutated V(H) genes, considered to evolve from pregerminal centre (GC) cells, have a worse outcome compared to cases showing mutated V(H) genes, that is, post-GC derived. Also, telomere length has been reported to be of prognostic significance in CLL. Interestingly, telomerase becomes activated during the GC reaction and an elongation of the telomeres occurs in GC B cells. We performed telomere length and V(H) gene analysis in a series of 61 CLL cases, in order to investigate if the unique telomere lengthening shown in GC B cells could reflect the telomere status in the two subsets of mutated and unmutated CLL. A novel association was found between V(H) gene mutation status and telomere length, since significantly shorter telomeres were demonstrated in the unmutated group compared to the mutated group (mean length 4.3 vs 6.3 kbp). Shorter telomeres also constituted a subgroup with a worse prognosis than cases with longer telomeres (median survival 59 vs 159 months). Furthermore, the Ig gene sequence data revealed that samples with high mutations frequency (>6%) had long telomeres ( approximately 8 kbp). Thus, both the telomere and V(H) gene mutation status in CLL appear linked, which may reflect the proliferative history of the clonal cells with regard to the GC reaction.

Aged↗
PubMed2001

On the functional role of muscarinic M2 receptors in cholinergic and purinergic responses in the rat urinary bladder.

The functional effects of muscarinic receptor and purinoceptor agonists and antagonists were studied on isolated strip preparations of the rat urinary bladder. The muscarinic "M3/M1-selective" receptor antagonist 4-diphenylacetoxy-N-methylpiperidine methobromide (4-DAMP) most conspicuously inhibited the carbachol-evoked contractile responses (pA2=9.8), while the muscarinic "M1-selective" receptor antagonist pirenzepine and the muscarinic "M2-selective" receptor antagonist methoctramine were less potent (pA2=7.0 and 6.5, respectively). Administration of 4-DAMP in combination with methoctramine in selective dosages gave no significant additional reduction of carbachol-evoked contractile responses. Adenosine 5'-triphosphate (ATP) elicited transient dose-dependent contractile responses and it caused relaxation of the carbachol-contracted detrusor strips. The relaxatory response was enhanced in the presence of methoctramine and furthermore, was attenuated by the adenosine receptor antagonist 8-p-sulfophenyltheophylline. Administration of 2-chloro-adenosine to pre-contracted strips tended to cause dose-dependent relaxations, which were significantly increased in the presence of methoctramine. The purinergic contractile response, on the other hand, was not affected by methoctramine. Thus, the results are consistent with the cholinergic contractile response in the rat urinary bladder being exerted via activation of muscarinic M3 receptors, while the muscarinic M2 receptors exerted a modulator effect on purine-evoked relaxations in the rat urinary bladder.

2-Chloroadenosine↗
PubMed2001

Effect of rodent diets on the sexual development of the rat.

Five rodent diets have been evaluated for their possible effect on the sexual development of the rat. Groups of 12 pregnant Alpk rats were fed one of the following combinations of diets during pregnancy and postnatally: RM3/RM1, AIN-76A/AIN-76A, RM3/AIN-76A, Teklad Global 2016 (Global)/Global and Purina 5001/Purina 5001. AIN-76A is phytoestrogen-free while the other diets contained varying amounts of phytoestrogens. The phytoestrogens genistein and daidzein were determined in the diets studied, and the concentrations found agreed with earlier estimates. RM3/RM1 was selected as the control group, as this has been used routinely in this laboratory for the past decade. Determinations were made in offspring of the times of vaginal opening and first estrus among the females, and of prepuce separation and testes descent among the males. At postnatal day (PND) 26 the females from 6 of the 12 litters were terminated and tissue weights measured. Males from 6 of the 12 litters were similarly studied at PND 68. Animals from the remaining litters were transferred to RM1 diet at PND 70. Termination of the study was at PND 128 (males) and PND 140 (females) when body weights and tissue weights were determined. Marked differences in body weight, sexual development, and reproductive tissue weights were observed for rats maintained on AIN-76A or Purina 5001, with only minimal effects among rats maintained on the Global diet. These comparisons were against RM3/RM1 as the reference diet. However, using Purina 5001 as the reference diet reversed the direction of the differences seen when using RM3/RM1 as the reference diet. The differences observed when using RM3/RM1 as reference diet occurred mainly postnatally. In addition, the fact that similar differences were seen for the phytoestrogen-free diet, AIN-76A, and the phytoestrogen-rich diet, Purina 5001, indicate that these effects are more likely to be caused by nutritional differences between the diets that then have centrally mediated effects on rodent sexual development, rather than individual dietary components affecting peripheral estrogen receptors (ER). This proposal is supported by abolition of the uterotrophic activity of AIN-76A and Purina 5001 (relative to RM3/RM1) in the immature rat by coadministration of the gonadotrophin-releasing hormone (GnRH) antagonist ANTARELIX: The present data indicate that choice of diet may influence the timing of sexual development in the rat, and consequently, that when evaluating the potential endocrine toxicity of chemicals, the components of rodent diets used should be known, and as far as is possible, controlled.

Age Factors↗
PubMed2000

Hospital readmissions. We'll meet again.

A 12-month study of emergency medical admissions at one trust suggests most readmissions could not be avoided. The re-admission rate within 28 days was 10 per cent, of which 5 per cent were found to be preventable. Readmissions were higher among smokers, men and people living in hostels. The study found no evidence of increased readmissions in winter.

Adolescent↗
PubMed1999

Evaluation of stimulation parameters on aortomyoplasty, using Latissimus Dorsi muscle in a goat model: an acute study.

OBJECTIVE: Dynamic aortomyoplasty using Latissimus Dorsi muscle (LDM) has been shown to improve myocardial function. However, systematic examination of the effects of stimulation parameters on aortic wrap function has not been done. Thus, the present study measures the direct effect of stimulation voltage, pulse train duration, frequency of the pulses, and the duration of the stimulation delay from R wave on the aortic wrap function. METHODS: In eight female goats, the left LDM was wrapped around the descending aorta. The muscle was then subjected to electrical stimulation, altering frequency of stimulation pulses (16.6, 20, 25, 33 and 50 Hz), amplitude (2, 4, 6, 8 and 10 V), and number of pulses (2, 4, 6, 8 and 10 pulses) in a train stimulation. Left ventricular, aortic pressure, and pressure generated by LDM on aorta (wrap pressure) was measured. The changes in hemodynamic parameters mentioned above were calculated and compared for different stimulation parameters during unassisted and assisted cardiac cycles. RESULTS: Aortomyoplasty counterpulsation using LDM provided significant improvement in wrap pressure (78 mmHg +/- 2), aortic diastolic pressure, and changes in aortic diastolic pressure from 2 to 4 V (P < 0.05). Further increase in amplitude did not make any significant improvements of the above mentioned parameters. Significant augmentation of wrap pressure (82 mmHg +/- 2), aortic diastolic pressure (79 mmHg +/- 3) and changes in aortic diastolic pressure (12 mmHg +/- 1) occurred at 6 pulses (P < 0.05). Other changes in number of pulses did not show any significant improvements. Significant improvement of wrap pressure (80 mmHg +/- 2), aortic diastolic pressure (73 mmHg +/- 3) and changes in aortic diastolic pressure (12 mmHg +/- 1) was observed with a frequency of 33 Hz. To examine a wide range of delays from the onset of the QRS complex to LDM stimulation, stimulation was delivered randomly. The exact delay was determined from the ECG signal and superimposed LDM stimulation pulses. CONCLUSIONS: In this study we present a new measurement, wrap pressure. We also present that in aortomyoplasty using LDM, the most significant improvement in wrap pressure, aortic diastolic pressure and changes in aortic diastolic pressure occurs when the stimulation consists of an amplitude of 4 V, a frequency of 33 Hz and a train stimulation of 6 pulses.

Animals↗
PubMed1998

Presynaptic muscarinic M1 and M2 receptor modulation of auriculotemporal nerve transmission in the rat.

Parotid secretory and vascular responses to electrical stimulation of the parasympathetic innervation were measured in anaesthetized rats. Stimulation was performed at 1, 10 and 40 Hz. Atropine (1.5 micromol/kg i.v.) almost abolished the secretion to stimulation of peptide depleted nerves at 40 Hz, thus confirming the existence of a pure cholinergic response. Atropine also reduced secretion by 74% during stimulation of non-depleted nerves at the same frequency. Selective blockade by the muscarinic M1 receptor antagonist pirenzepine and by the muscarinic M2 receptor antagonist methoctramine was found to occur at doses (50 nmol/kg i.v. and of 300 nmol/kg i.v., respectively) that did not inhibit the responses to exogenous acetylcholine. In the presence of methoctramine, the nerve-evoked fluid responses were increased by 200% at 1 Hz independently of the total number of impulses (10-300), suggesting that M2 receptor activation normally has an inhibitory effect on transmitter release. The magnitude of the increase was inversely related to frequency of stimulation, and changes in the secretory responses occurred at 40 Hz only when non-depleted nerves were stimulated over the longest period employed. The fluid response then increased by 35% and protein concentration by 200%. The vasodilator responses increased at 1 and 10 Hz, but not at 40 Hz. Pirenzepine reduced the secretory and vascular responses at 10 and 40 Hz but only during stimulation over short periods of time. This suggests that M1 receptor activation normally has a facilitatory effect on neurotransmitter release. During stimulation of non-depleted nerves at 10 Hz for 10 impulses, the fluid response was reduced by 29% and the protein concentration by 26%. When the peptide depleted nerves were stimulated at 10 Hz, pirenzepine also reduced the fluid response (by 43%), but not the protein concentration. It is concluded that the release of transmitter from postganglionic nerve fibres in the rat auriculotemporal nerve is modulated by presynaptic muscarinic receptors. Muscarinic M1 receptors normally facilitate cholinergic and peptidergic transmission during short, intense stimulation. On the other hand, muscarinic M2 receptors normally inhibit cholinergic transmission at low frequencies; at higher frequencies, peptidergic transmission is also inhibited, but only after some delay.

Acetylcholine↗
PubMed1998

Prejunctional facilitatory and inhibitory modulation of parasympathetic nerve transmission in the rabbit urinary bladder.

Release of [3H]choline and muscle contraction in response to electrical field stimulation were measured from rabbit detrusor muscle strips previously loaded with [3H]choline. The importance of different stimulation frequencies (1 and 10 Hz) for activating either facilitatory or inhibitory prejunctional effects was examined in the presence of muscarinic and adrenergic (alpha2) receptor selective substances. At 1 Hz, neither [3H]choline overflow nor contraction was affected by the M1-selective receptor antagonist pirenzepine (10(-7) M), whereas overflow and contraction decreased at 10 Hz. The M1-selective receptor agonist McN-A-343 (10(-6) M) caused no significant changes except for reducing contractions at 10 Hz. The M2-selective receptor antagonist methoctramine (10(-6) M), on the other hand, increased overflow as well as contraction at both frequencies, most conspicuously at 1 Hz. Atropine (10(-7) M) caused a significant increase with respect to overflow only at 1 Hz, while quite the opposite effect occurred with respect to contractions (reduced only at 10 Hz). Clonidine (10(-6) M) induced inhibition of [3H]choline overflow at 10 Hz only, but without significantly changing contractile responses. The results show that in the rabbit urinary bladder a muscarinic autoreceptor mediated inhibition (M2) of the transmitter release dominates during low frequency stimulation and that a facilitation (M1) may be present at stimulations with higher frequencies. However, this amplification may also be influenced by alpha2-adrenoceptor mediated inhibition.

Adrenergic Agents↗
PubMed1998

Parasympathetic non-adrenergic, non-cholinergic mechanisms in salivary glands and their role in reflex secretion.

Parasympathetic atropine-resistant vasodilatation is a well-known phenomenon in salivary glands. Less well known is the fact that there also exists an atropine-resistant secretory response to parasympathetic stimulation: some glands secrete saliva, albeit at a reduced rate, whereas others just release protein and acinar secretory granules. A number of peptides, including vasoactive intestinal peptide (VIP) and substance P, are likely to be involved in the so called non-adrenergic, non-cholinergic (NANC) transmission of the parasympathetic secretory impulses. We here report a series of experiments where we have found these NANC-mechanisms to be mobilized during reflex secretion. Loss of acinar granules, morphometrically assessed, and reduction in glandular amylase activity indicated secretory activity in the parotid gland of the conscious rat, in the presence of atropine and adrenoceptor antagonists, in response to food intake. As judged by these indices, the NANC mechanisms were potentially responsible for the whole parasympathetic response and, thus, for the major part of the marked response in the absence of the antagonists. Furthermore, the reflex mobilization of the NANC mechanisms depended on mastication rather than on taste, and involved the release of VIP and substance P. The results presented give weight to a physiological role for these mechanisms, and support the idea that, under normal conditions, the NANC mechanisms act in concert with cholinergic and adrenergic mechanisms to generate the most purposeful secretory reflex response to the afferent stimulation.

Animals↗
PubMed1997

Bovine immunodeficiency virus tat gene: cloning of two distinct cDNAs and identification, characterization, and immunolocalization of the tat gene products.

cDNAs encoding the bovine immunodeficiency virus (BIV) transactivator gene (tat) were cloned from virally infected cells and characterized. BIV expresses two distinct tat mRNAs composed of three exons that are derived by alternative splicing. The BIV tat mRNA splice variants encode Tat proteins of 103 (Tat103) and 108 (Tat108) amino acids. The Tat103 coding region is specified only by exon 2, while that of Tat108 is specified by a truncated exon 2 and the first 30 nt of exon 3. Thus, the first 98 amino acids of each Tat are identical, and have amino terminal, cysteine-rich, conserved core, basic, and carboxyl-terminal domains similar to Tats encoded by primate lentiviruses. BIV-infected bovine cells express a 14-kDa phosphorylated Tat protein identical in size to recombinant Tat expressed in bacteria. BIV Tat was shown to localize exclusively in the nucleoli of virally infected and Tat-expressing cells. Reporter gene assays indicated that Tat103 and Tat108 can strongly transactivate the BIV long terminal repeat (LTR) in virally permissive canine Cf2Th and nonpermissive HeLa and mouse NIH 3T3 cells, but not in permissive lapine EREp cells. However, an intact BIV tat gene is required for viral replication in both Cf2Th and EREp cells. Strong LTR activation by BIV Tat requires a TAR (transactivation responsive) element delimited by viral nt +1 to +31 and the Tat basic domain. BIV Tat strongly cross-transactivates the HIV-1 LTR in a TAR-dependent manner in Cf2Th, but not in EREp, HeLa, or NIH 3T3 cells. In contrast, strong, TAR-dependent cross-transactivation of the BIV LTR by HIV-1 Tat could not be demonstrated in any of these cell types. In Cf2Th cells Tat108 effects a moderately stronger transactivation of the BIV LTR than Tat103, indicative of a functional difference in BIV Tat proteins encoded by the mRNA splice variants. The present studies demonstrate that BIV Tat parallels the primate lentiviral Tats in structure and biochemistry but is not interchangeable with the latter.

3T3 Cells↗
PubMed1997

Nitric oxide synthase immunoreactive nerves in rat and ferret salivary glands, and effects of denervation.

Nitric oxide has been implicated in mechanisms mediating nerve-evoked vasodilatory and secretory responses in salivary glands. In the present study, the occurrence and distribution of nitric oxide synthase (NOS)-immunoreactive nerves in ferret and rat salivary glands were investigated using immunocytochemistry with rabbit and sheep NOS antisera, and using NADPH-diaphorase enzyme histochemistry. In the parotid, submandibular and sublingual glands of the rat and the ferret, NOS-immunoreactive varicose terminals encircled acini and arteries of various sizes. In the ferret, collecting ducts were also supplied with NOS-immunoreactive fibres. In the rat, only the granular ducts of the submandibular gland were supplied with such fibres. The NOS-immunoreactive innervation of acinar cells was more abundant in the rat than in the ferret, whereas the opposite was true for the innervation of blood vessels. No NOS immunoreactivity was observed in the vascular endothelium. In both species, NOS-positive ganglionic cell bodies were found in the hilar regions of the submandibular and sublingual glands, whereas none could be detected in the parotid glands. NADPH-diaphorase reactivity had the same neuronal distribution as NOS immunoreactivity and, in addition, NADPH-diaphorase reactivity was expressed in ductal epithelium. Neither sympathetic denervation (by removal of the superior cervical ganglion) nor treatment with the sensory neurotoxin capsaicin reduced the NOS-immunoreactive innervation of the parotid gland. However, parasympathetic denervation (by cutting the auriculo-temporal nerve) caused an almost total disappearance of the NOS-immunoreactive innervation. The present findings provide a morphological background to the suggested role of nitric oxide in parasympathetic secretory and vascular responses of salivary glands.

Animals↗
PubMed1997

Pituitary adenylate cyclase activating peptide (PACAP) in salivary glands of the rat: origin, and secretory and vascular effects.

Pituitary adenylate cyclase activating peptide (PACAP)-38, injected i.v. to the anaesthetized rat, evoked secretion of saliva from the three major salivary glands, the submandibular glands responding with the greatest and the sublingual glands with the smallest volumes. The parotid saliva was rich in amylase and protein. In vitro, pieces of parotid and submandibular gland tissues released K+ and protein in response to PACAP-38, with atropine and adrenoceptor antagonists present. The blood flow in the submandibular gland increased in response to PACAP-38, despite a marked fall in mean aortic blood pressure. PACAP is a vasoactive intestinal peptide (VIP)-like neuropeptide. A comparison between the two peptides showed PACAP-38 to be more effective than VIP with respect to vascular responses and less or equi-effective with VIP with respect to the secretory responses, thus suggesting the involvement of PACAP type I and type II receptors, respectively PACAP-38 and -27 were present in the parotid gland as judged by radioimmunoassay, the concentration of the former being about twice that of the latter. Parasympathetic denervation, by cutting the auriculo-temporal nerve, reduced the total parotid gland contents of PACAP-38 and -27 by 23 and 44%, respectively (compared with a previously demonstrated 95% reduction of VIP). Sympathetic denervation, section of the facial nerve or treatment with the sensory neurotoxin capsaicin did not affect the content of PACAP. The difference in efficacy between PACAP and VIP in the vascular and secretory responses as well as the difference in localization suggest that the two peptides play different physiological roles in the salivary glands.

Animals↗