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Biomedical subjects

G Tobin

Publications and source records attributed to G Tobin.

At least 55 records · Page 3Linked to original sources
PubMed1994

Masticatory-salivary reflexes mobilize non-adrenergic, non-cholinergic secretory mechanisms in parotid glands of conscious rats.

All rats were maintained on liquid diet, prepared from their ordinary hard pelleted diet, for a week, then fasted 32-33 h and subsequently either fed liquid or pelleted diet for 60-90 min or serving as non-fed controls. Both the fed and the non-fed animals had received atropine and alpha- and beta-adrenoceptor antagonists 15 min before the test. The rats given the liquefied chow consumed about twice as much as those given the hard chow. In the parotid glands of the rats given hard chow the number of acinar granules and the total amylase activity were reduced, by 50 and 70%, respectively, as compared with the glands of control rats. In the parotid glands of the rats given liquefied chow the number of acinar granules and the total activity of amylase remained unchanged. The results suggest that non-adrenergic, non-cholinergic secretory mechanisms of the rat parotid gland participate in masticatory-salivary reflexes.

Adrenergic alpha-Antagonists↗
PubMed1994

Electrophoretic analysis of cat parotid saliva in response to parasympathetic stimulation or infusion of bethanechol.

The protein constituents of cat parotid saliva evoked by parasympathetic stimulation or the infusion of bethanechol have been compared by sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE). The SDS-PAGE patterns were highly reproducible for an individual cat and revealed up to 30 polypeptide bands in microlitre volumes of unconcentrated saliva. Only minor and predominantly quantitative differences were detected in the salivary protein composition of different cats. SDS-PAGE demonstrates quantitative rather than qualitative changes in the protein composition of saliva evoked in response to different stimuli. The latter included preliminary observations on the effect of vasoactive intestinal peptide (VIP) on the bethanechol-evoked response.

Animals↗
PubMed1993

Electrophoretic analysis of stimulated cat parotid saliva.

The proteins of parasympathetically stimulated cat parotid saliva were analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and high resolution two-dimensional electrophoresis (2-DE). SDS-PAGE revealed up to 30 polypeptide bands in microliter volumes of unconcentrated saliva. The patterns were highly reproducible and characterized by prominent bands of M(r) 57,000, M(r) 30,000 and M(r) 15,000. The major protein (M(r) 30,000) appeared as a dimer (M(r) 60,000) when electrophoresed under non-reducing conditions but dissociated into its monomeric form when the SDS concentration of the denatured samples was increased from 1 to 5%. This indicates a noncovalent association. The protein patterns of saliva from different cats differed slightly but sequential samples from the same cat (collected during 90 min of stimulation) showed little change in protein pattern apart from a fall in total protein content. Following 2-DE, the major protein (M(r) 30,000) appeared as a complex array of at least eight spots in two tiers (pI 5.2-6.2; M(r) 28,000 and 32,000). The characteristics of this protein are discussed with reference to allergy to cats.

Animals↗
PubMed1993

Parasympathetic non-adrenergic, non-cholinergic mechanisms in reflex secretion of parotid acinar granules in conscious rats.

1. Female adult rats were subjected to sympathetic denervation of the parotid glands by bilateral removal of the superior cervical ganglion 10-12 days before acute experiments. The sympathectomy was in some of the experimental groups combined with either bilateral adrenal medullectomy, treatment with the sensory neurotoxin capsaicin or parasympathetic denervation of the gland by cutting the auriculotemporal nerve. 2. Food but not water was withheld for 29-32 h before acute experiments. All animals were given an intraperitoneal injection of phentolamine (2 mg kg-1) and propranolol (1 mg kg-1) and, when appropriate, also atropine (1 mg kg-1). Then the experimental animals were fed their ordinary food of hard chow for 60-90 min. Thereafter, these animals and their non-fed controls were killed, and the parotid glands were removed and used for either morphometric assessment or measurement of amylase activity. 3. In the atropinized rats subjected to sympathectomy alone, eating reduced the numerical density of acinar secretory granules by 50% and the total activity of amylase by 55%; the corresponding figures were, when sympathectomy was combined with adrenal medullectomy, 51 and 63%. Also, in atropinized animals subjected to sympathectomy and capsaicin pretreatment, eating reduced the numerical density of acinar granules and the total amylase activity, in this case by 45 and 35%, respectively. 4. In the atropinized rats subjected to sympathectomy and parasympathectomy, eating caused no change in the numerical density of acinar granules but reduced the total amylase activity by 35%. 5. In the non-atropinized rats subjected to sympathectomy alone, eating reduced the numerical density of acinar granules by 22%, while there was no change in the total amylase activity. 6. In conclusion, eating evoked a reflex activation of the sympathectomized parotid gland that engaged non-adrenergic non-cholinergic receptors of the acinar cells. The present results give weight to a physiological role for non-adrenergic non-cholinergic parasympathetic mechanisms in salivary secretion under reflex conditions.

Adrenal Medulla↗
PubMed1992

Parasympathetic NANC-secretion of saliva in the mink, and effects of substance P and VIP.

In both parotid and submandibular glands a parasympathetic non-adrenergic, non-cholinergic (NANC) nerve-evoked secretion of saliva was demonstrated. Saliva evoked by exogenous substance P was poor in protein, while saliva evoked by VIP was protein-rich. In a subthreshold dose for fluid secretion VIP released protein and potentiated the responses elicited by substance P, particularly regarding the output of protein. The two neuropeptides may contribute to the parasympathetic NANC secretion of saliva in the mink. Further, agonists responsible for the secretory NANC response are also likely to contribute to the secretory response of the glands to parasympathetic stimulation in the absence of autonomic receptor blockade in this species.

Adrenergic alpha-Antagonists↗
PubMed1992

Functional analysis of the rat insulin-like growth factor I gene and identification of an IGF-I gene promoter.

Insulin-like growth factor I (IGF-I) mediates many of the systemic growth-promoting effects of growth hormone and also functions as a locally acting growth stimulator. In mammals, IGF-I gene expression is complicated, as the gene is transcribed and processed into multiple mRNAs (ranging in length from less than 1 to nearly 7.5 kb) that encode at least two protein precursors. As a step toward understanding the regulation of IGF-I, we report the complete organization of the rat IGF-I gene, including identification of the structural determinants for all IGF-I mRNA species, and an initial functional analysis of its promoters. The gene is composed of 6 exons distributed over nearly 80 kb of chromosomal DNA and is structurally heterogeneous. Several transcription start sites were identified within IGF-I exons 1 and 2, adjacent to presumptive promoters 1 and 2, respectively, and at least three polyadenylation sites were mapped to exon 6. To test promoter function, fusion genes were constructed linking fragments of IGF-I DNA to a reporter plasmid. Chimeric genes containing at least 395 bp of DNA from the 5'-flanking region of exon 1 enhanced luciferase activity after transfection into the IGF-I-producing SK-N-MC cell line, while fusion plasmids containing up to 1,300 bp of DNA from the 5'-flanking region of exon 2 were inactive. Relative levels of IGF-I mRNAs containing exons 1 or 2 varied among different rat tissues, although in response to acute or chronic growth hormone treatment both classes of transcripts were induced coordinately in rat liver. These observations represent the first thorough characterization of a mammalian IGF-I gene, and provide a starting point for defining the mechanisms by which growth hormone and other trophic factors regulate IGF-I gene expression.

Amino Acid Sequence↗
PubMed1991

Atropine-resistant submandibular responses to stimulation of the parasympathetic innervation in the anaesthetized ferret.

1. Submandibular salivary and vascular responses to stimulation of the peripheral end of the chorda-lingual nerve at 20 Hz continuously for 60 min were investigated in anaesthetized ferrets, in which the sympathetic innervation to the gland was cut, in the presence and absence of atropine (2.0 mg kg-1). 2. Both the increase in submandibular salivary flow and protein output, which occurred in response to nerve stimulation, were substantially reduced following the administration of atropine, the latency was greatly increased thereby, and both responses were more transient but neither was abolished by atropine. The fall in submandibular vascular resistance was not significantly affected by atropine, either in respect of extent or duration. 3. Chorda-lingual stimulation produced an increase in the output of vasoactive intestinal peptide (VIP), substance P (SP) and calcitonin gene-related peptide (CGRP) in the submandibular venous effluent blood. Each of these responses was maximal within the first 10 min after the onset of stimulation and declined thereafter. The time-scales of both the CGRP and SP responses were similar to those of the atropine-resistant secretory responses, both being quite short-lived, whereas the output of VIP (like the atropine-resistant vascular response) was significantly greater than the basal value throughout the whole of the 60 min period of stimulation. 4. The CGRP response was completely abolished by pre-treatment with atropine, whereas the outputs of both VIP and SP were significantly enhanced thereby. Both the submandibular vascular and secretory responses to chorda-lingual stimulation were almost completely suppressed following the administration of hexamethonium, and there was then no detectable release of peptidergic agonists from the gland. 5. The atropine-resistant submandibular salivary secretory responses were completely abolished by pre-treatment with a tachykinin inhibitor [( D-Arg1, D-Cl2 Phe5, Asn6, D-Trp7,9, Nle11]-SP; 0.75 mg kg-1) without affecting the fall in submandibular vascular resistance. 6. Following pre-treatment with hexamethonium, I.V. bolus injections of methacholine, SP and CGRP elicited increases in submandibular blood flow and secretion of saliva. VIP caused an increase in blood flow without overt secretion, although it is known to increase secretion of protein and to potentiate the secretory response to SP. Taken together, all these results are consistent with the contention that VIP contributes to the vasodilator response to stimulation of the para-sympathetic innervation in this gland and that both SP and CGRP are likely to contribute to the secretory response.

Animals↗
PubMed1991

Risks of premature death and cancer predicted by body weight in early adult life.

In a study of 30 months duration, involving 600 male and 600 female Wistar rats fed on 12 different diets/dietary regimes, none of which involved deliberate exposure to any known genotoxic carcinogen, highly significant between-group differences were observed in survival and incidence of various neoplastic and non-neoplastic diseases. A full report of the findings is being prepared. Here we report that, irrespective of diet or dietary regime, there were highly significant correlations of body weight at 29 weeks of age with premature death (P less than 0.0001 in both males and females), with development of benign or malignant neoplasm of any site (P less than 0.0001 in males and P less than 0.01 in females) and with development of malignant neoplasm at any site (P less than 0.0001 for sexes combined). Numerous kinds of neoplasm contributed to these overall correlations. The most significant were pituitary tumour (P less than 0.0001), mammary gland tumour (P less than 0.0001), squamous or anaplastic carcinoma of the jaw (P less than 0.001), and subcutaneous mesodermal tumours (P less than 0.05). The 20% of rats that were heaviest at 29 weeks were more than twice as likely to die prematurely than the lightest 20% (2.56 times--males, and 2.11 times--females), and almost twice as likely to develop a malignant tumour (1.87 times for the sexes combined). These findings have important implications for the design and interpretation of carcinogenicity tests in rodents and of laboratory and human studies of relationships between diet, ageing-related degenerative diseases, and cancer.

Animals↗
PubMed1990

VIP-containing nerve fibres in the submandibular gland of the dog and protein secretion in vitro in response to VIP.

Previously, administration of VIP has been shown to elicit no flow of saliva from the submandibular gland of the dog. However, in the present study we found VIP to cause release of protein in vitro from canine submandibular gland tissue. Furthermore, VIP-containing nerve fibres were demonstrated in large numbers in association with acini. Thus, VIP may be involved in the nervous regulation of salivary protein secretion in the dog.

Animals↗
PubMed1990

Protein secretion in salivary glands of cats in vivo and in vitro in response to vasoactive intestinal peptide.

In anaesthetized cats exogenous vasoactive intestinal peptide failed to elicit any secretion of saliva from the submandibular and parotid glands. However, protein release from both glands occurred in response to VIP in the presence of alpha- and beta-adrenoceptor blocking agents and was dose-dependent. This response was revealed by means of a subsequent washout flow of saliva evoked by intravenous injections of methacholine or stimulations of the parasympathetic innervation. The submandibular glands responded to vasoactive intestinal peptide at a lower dose than the parotid glands. In the presence of atropine (but in the absence of adrenoceptor blockers), stimulation of the parasympathetic chorda-lingual nerve, which of itself elicited no secretion of saliva, contributed to the release of protein within the submandibular gland, since the output of protein in response to a subsequent stimulation of the sympathetic innervation was increased. Vasoactive intestinal peptide administered in combination with methacholine or during ongoing parasympathetic nerve-induced salivary secretion revealed positive interactions, particularly with respect to protein release. In-vitro protein release in response to vasoactive intestinal peptide was also demonstrated by perfusing small pieces of the two glands in the presence of muscarinic and adrenoceptor blockers. As in vivo, submandibular tissue responded at a lower concentration of vasoactive intestinal peptide than the parotid tissue. One to two weeks after combined parasympathetic and sympathetic denervation of the parotid glands, the glands were sensitized to vasoactive intestinal peptide when tested in vitro. It is concluded that vasoactive intestinal peptide or a structurally related peptide is a potential transmitter in the parasympathetic control of protein secretion in salivary glands of cats.

Animals↗
PubMed1990

Submandibular responses to stimulation of the parasympathetic innervation in bursts in the anaesthetized ferret.

1. Submandibular salivary and vascular responses to different patterns of stimulation of the parasympathetic innervation have been investigated in anaesthetized ferrets in the presence and absence of atropine. 2. At low stimulus frequencies likely to fall within the physiological range (0.5-2.0 Hz continuously; 5.0-20.0 Hz in 1 s bursts at 10 s intervals) secretion of fluid and protein were both potentiated by the bursting pattern of stimulation and the latency of the secretory response was reduced. Over a somewhat lower range (0.5-1.0 Hz continuously; 5.0-10.0 Hz in bursts) the submandibular vascular response was also significantly potentiated by employing this intermittent pattern of stimulation. Above these frequency ranges no such potentiation occurred. 3. Pre-treatment with atropine (2.0 mg kg-1) blocked the submandibular secretory responses to stimulation of the chorda-lingual nerve at these low frequencies and the residual responses at higher frequencies were not significantly affected by changing the pattern of stimulation. The vascular response was somewhat reduced after atropine but that which persisted was enhanced by stimulating in bursts. 4. It is concluded that the release of some transmitter from postganglionic terminals in the submandibular gland of the ferret must be potentiated by the arrival of action potentials at short intervals and possible mechanisms are considered.

Anesthesia, Intravenous↗
PubMed1990

Is increased metabolism in rats in the cold mediated by the thyroid?

1. In the rat variation of metabolic heat production is the principal effector of thermoregulation. There is a continuous relationship between ambient temperature and metabolic rat over the whole range of tolerable environmental temperature. The mechanism that controls metabolic rate is unknown; this paper reports an attempt to test whether thyroid hormones provide the controlling pathway. 2. First, the changes in metabolic rate and in the plasma concentrations of thyroid stimulating hormone (TSH), triiodothyronine (T3) and thyroxine (T4) were measured in rats living in a controlled environment, first at 23 degrees C and then at 6 degrees C. Metabolic rate increased from approximately 290 to 470 kJ day-1 when the temperature was lowered, a factor of ca 1.6, and the diurnal rhythm disappeared. The concentration of TSH increased from approximately 320 to 450 ng ml-1 (with loss of diurnal rhythm) and of T3 from ca 0.7 to 1.0 nmol l-1, a factor of ca 1.4 in each case. T4 concentration did not change. 3. Next, a dose schedule of T3 was found that, when injected I.V. via indwelling jugular cannulae in the same rats in an environment at 23 degrees C, maintained an increase in T3 concentration rather greater than had been found at 6 degrees C. 4. This dose of T3, given to the same rats at 23 degrees C, did not affect metabolic rate (or its diurnal pattern). 5. It is therefore unlikely that the increase in T3 concentration evoked the increase in metabolic rate when ambient temperature was changed from 23 to 6 degrees C; and therefore that the thyroid controls variation of metabolic rate in 'everyday' thermoregulation in the rat.

Animals↗
PubMed1990

A novel human insulin-like growth factor I messenger RNA is expressed in normal and tumor cells.

We have identified and characterized a novel human insulin-like growth factor I (IGF-I) precursor from the transplantable T61 human breast cancer xenograft and from normal liver. The mRNA encoding this precursor contains a 5'-untranslated region that is 83% identical to the corresponding region of a previously described variant rat IGF-I. The nucleotide sequence of the cloned cDNA predicts an IGF-IA protein precursor of 137 amino acids, including a 32 residue signal peptide, 70 amino acid IGF-I, and a 35 residue COOH-terminal extension or E peptide. The exon encoding this variant maps in the genome between IGF-I exons 1 and 2, in a similar location to the homologous rat exon 1a. The rat and human exons 1a are 59% identical over 1443 nucleotides, with DNA sequence conservation occurring in a mosaic pattern. Human IGF-I mRNAs encoding this novel exon are expressed in liver, T61 tumor cells, and in an ovarian carcinoma cell line, NIH OVCAR3. These studies demonstrate that as in the rat, the human IGF-I gene contains six exons that are variably processed into multiple IGF-I mRNAs. The mechanisms responsible for generating different IGF-I mRNAs thus appear to be conserved among mammalian species.

Amino Acid Sequence↗
PubMed1989

Depletion of large dense-cored vesicles from parasympathetic nerve terminals in rat parotid glands after prolonged stimulation of the auriculotemporal nerve.

Large dense-cored vesicles (60-100 nm in diameter) have been assessed electron-microscopically in terminal parasympathetic axons at acinar neuro-effector sites in rat parotid glands. Their numbers in control unstimulated glands have been compared with those in the contralateral glands of the same animals after prolonged nerve stimulation. Bilateral postganglionic sympathectomy had been undertaken 4-6 weeks previously to remove adrenergic axons from the glands. Stimulation of the postganglionic parasympathetic nerve to the gland--the auriculotemporal nerve--for 80 min at 40 Hz caused a significant depletion of large dense-cored vesicles from the terminal axons. This depletion corresponded in time and magnitude to the depletion of vasoactive intestinal peptide and substance P from the glands that had been found previously to occur under identical conditions. This adds support to the belief that the neuropeptides are stored in such vesicles and that these vesicles release their contents at neuro-effector sites as a result of propagated impulse formation in the axons.

Animals↗
PubMed1989

Effects of capsaicin pretreatment on neuropeptides and salivary secretion of rat parotid glands.

1. 'Atropine-resistant' secretion of saliva in response to parasympathetic stimulation may reflect antidromic activation of sensory nerve fibres. In this investigation, the effect of pretreatment in the rat with capsaicin (total dose of 125 mg kg-1, s.c.), was determined. 2. In the parotid glands substance P (SP)/calcitonin gene-related peptide (CGRP)-containing nerve fibres around ducts and blood vessels disappeared after capsaicin, while periacinar SP-containing fibres (devoid of CGRP) and CGRP-containing fibres (devoid of SP) remained. Vasoactive intestinal peptide (VIP)-containing nerve fibres seemed to be unaffected. The parotid content of SP and CGRP was reduced by 11 and 36% respectively, while that of VIP remained unchanged. 3. The weights of the parotid glands and their sensitivity to the secretagogues methacholine and SP, injected intravenously, were unchanged as was the response to stimulation of the auriculo-temporal nerve in the presence and absence of atropine. 4. In contrast to capsaicin pretreatment, parasympathetic denervation of the parotid gland reduced the weight of the gland and produced an increase in the response to methacholine and SP. 5. For comparison, the effectiveness of the capsaicin treatment on neuropeptide content was determined in the urinary bladder. The bladder of capsaicin-pretreated rats increased in weight (21%) and in VIP content (31%), while the content of SP and CGRP was reduced by 86 and 94%, respectively. SP- and CGRP-containing nerve fibres were virtually eliminated, while VIP-containing nerve fibres seemed unaffected. 6. In conclusion, antidromic activation of primary afferent (capsaicin-sensitive) C-fibres does not contribute significantly to the 'atropine-resistant' secretory response of the parotid gland to stimulation of the parasympathetic nerve.

Animals↗
PubMed1989

Spermidine/spermine-N1-acetyltransferase activity in isoprenaline-stimulated rat salivary glands.

In parotid, sublingual and submaxillary glands stimulated by continuous intravenous infusion of isoprenaline at various doses for 3 h, the concentrations of the polyamines putrescine, spermidine, spermine and N1-acetylspermidine as well as the activities of ornithine decarboxylase and spermidine/spermine-N1-acetyltransferase were determined. Ornithine decarboxylase is the enzyme that catalyses the formation of putrescine from ornithine. The most striking effect was observed in parotid glands. Here, the beta-adrenergic agonist increased the activity of spermidine/spermine-N1-acetyltransferase markedly, but only slightly (if at all) that of ornithine decarboxylase. It also increased the concentrations of N1-acetylspermidine and putrescine markedly. The result obtained in this gland indicates interconversion of higher polyamines to putrescine.

Acetyltransferases↗