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Biomedical subjects

C M Kuhn

Publications and source records attributed to C M Kuhn.

At least 73 records · Page 4Linked to original sources
PubMed1989

Opiate antagonist treatment reinstates estrous cycles in middle-aged persistent-estrous rats.

Middle-aged female rats display luteinizing hormone (LH) surge deficits and cycle irregularity followed by the onset of persistent estrus (PE). The central nervous system has been identified as a primary locus of failure in PE rats, but the particular neural elements involved have not been determined. The goal of the present study was to identify a role for endogenous opioid peptides (EOP) in age-related acyclicity by evaluating the effect of opiate antagonist treatment on vaginal cytology in PE rats. PE rats were administered, s.c., saline (SAL), naloxone (NAL) or naltrexone (NTX) once daily for 20 days, or repetitively on Day 1 and on successive proestrus days if cyclicity was resumed. Single NTX (50 mg/kg), but not NAL (2 mg/kg), treatment interrupted the PE state in almost half of treated animals. Daily or repetitive proestrus NTX (10 mg/kg) treatment interrupted PE more frequently, and many animals displayed repeated estrous cycles and ovulation. Afternoon LH surges were observed after initial NTX treatment in animals displaying PE interruption. This demonstration that LH surges and ovulatory cycles can be reinitiated in PE rats with NTX suggests that dysfunction in the 'brake' on EOP secretion during proestrus may be one of the neuroendocrine impairments mediating acyclicity in aging female rats.

Aging↗
PubMed1989

Muscarinic stimulation and antagonism and glucoregulation in nondiabetic and obese hyperglycemic mice.

Plasma glucose and insulin responses to a muscarinic agonist (bethanechol chloride) and a muscarinic antagonist (atropine) were evaluated in obese C57BL/6J ob/ob mice and in lean C57BL/6J + /? mice. In lean +/? mice, plasma glucose decreased in response to 1 and 2 micrograms/g bethanechol chloride, whereas insulin increased significantly. In ob/ob mice, insulin increased remarkably in response to bethanechol administration (saline, 632 +/- 80 microU/ml; 2 micrograms/g bethanechol chloride, 1794 +/- 97 microU/ml; n = 10), but surprisingly, plasma glucose also rose significantly (saline, 230 +/- 14 mg/dl; 2 micrograms/g bethanechol chloride, 363 +/- 18 mg/dl, n = 10). This exaggerated hyperglycemia in ob/ob mice was not associated with significant changes in plasma glucagon. Furthermore, administration of propranolol hydrochloride did not diminish bethanechol chloride-induced hyperglycemia in ob/ob mice. Administration of atropine (2.5, 5, and 10 mg/kg body wt) induced a significant decrease in plasma insulin without changes in plasma glucose in ob/ob mice, whereas neither plasma insulin nor plasma glucose changed in lean mice. Finally, conversion of [14C]alanine to glucose was increased in ob/ob mice after bethanechol chloride administration, indicating that muscarinic stimulation increases gluconeogenesis in an animal model of type II (non-insulin-dependent) diabetes.

Animals↗
PubMed1988

Relative ontogeny of opioid and catecholaminergic regulation of thyrotropin secretion in the rat.

In order to study the ontogeny of TSH regulation in the rat, we have compared TSH secretion in neonatal and adult rats after treatment with morphine, TRH and apomorphine, clonidine, and exposure to cold. Apomorphine attenuated exogenous TRH-induced TSH release in both neonatal and adult rats. Morphine suppressed TSH levels at every age tested. Although clonidine and cold exposure elicited TSH secretion in adults, neonatal rats did not respond to either treatment. These findings suggest that opioid and dopaminergic controls of TSH release mature before central noradrenergic regulation in developing rats. This lack of noradrenergic control may account for the absence of the response to cold exposure in the neonate.

Aging↗
PubMed1988

Opioid inhibition of luteinizing hormone release declines with age and acyclicity in female rats.

The current study assesses changes in opioid inhibition of LH secretion with age in female rats. We administered naloxone (NAL; 2 mg/kg, iv) to regularly cycling estrous rats of three age groups and measured serum LH in serial samples drawn from intraatrial catheters before and after treatment. The serum LH rise 10 min after NAL treatment in 4- to 6-month-old rats was significantly reduced (P less than 0.01) compared with that in 1.5- to 3-month-old animals, and no LH response was observed in 8- to 11-month-old rats. On early proestrus, LH secretion was also reduced 10 min after NAL treatment in older vs. younger rats, but all groups demonstrated belated LH rises 1 h after treatment during proestrus. Persistent estrous (PE) rats released less LH after NAL treatment than age-matched estrous rats (P less than 0.025). Higher dose NAL treatment did not increase LH release in estrous or PE rats. These results support the hypothesis that opioid inhibition of LH secretion diminishes with age in cycling rats. Furthermore, opioid tone is a function of estrous state as well as age. PE rats have lower opioid tone than cycling animals of the same age. Our findings suggest a possible role of diminished opiate tone in reproductive senescence.

Aging↗
PubMed1988

Diet-induced type II diabetes in C57BL/6J mice.

We investigated the effects of diet-induced obesity on glucose metabolism in two strains of mice, C57BL/6J and A/J. Twenty animals from each strain received ad libitum exposure to a high-fat high-simple-carbohydrate diet or standard Purina Rodent Chow for 6 mo. Exposure to the high-fat, high-simple-carbohydrate, low-fiber diet produced obesity in both A/J and C57BL/6J mice. Whereas obesity was associated with only moderate glucose intolerance and insulin resistance in A/J mice, obese C57BL/6J mice showed clear-cut diabetes with fasting blood glucose levels of greater than 240 mg/dl and blood insulin levels of greater than 150 microU/ml. C57BL/6J mice showed larger glycemic responses to stress and epinephrine in the lean state than AJ mice, and these responses were exaggerated by obesity. These data suggest that the C57BL/6J mouse carries a genetic predisposition to develop non-insulin-dependent (type II) diabetes. Furthermore, altered glycemic response to adrenergic stimulation may be a biologic marker for this genetic predisposition to develop type II diabetes.

Animals↗
PubMed1988

Physiological responses to catecholamine infusions in type A and type B men.

To determine whether there are basic biological differences between Type A and Type B men, we compared hemodynamic, electrophysiologic and neuroendocrine responses to equipotent doses of isoproterenol (ISO) and norepinephrine (NE) in 10 Type A and 10 Type B men ages 18 to 29. Results showed equal hemodynamic and neuroendocrine responses to graded ISO doses in Type A and Type B individuals. In contrast, Type A men showed a more prolonged decrease in electrocardiographic T-wave amplitude (TWA) than did Type B men. Post hoc analyses of the correlates of TWA recovery during high-dose ISO infusion provide preliminary evidence for a more robust parasympathetic antagonism of sympathetic nervous system effects in Type B men, especially those with low scores on the Cook-Medley Ho scale. These findings suggest that, in addition to cognitively mediated increases in sympathetic nervous system reactivity, Type As may also be placed at increased risk of developing coronary heart disease by reduced levels of parasympathetic antagonism of sympathetic effects.

Adolescent↗
PubMed1988

Effects of propranolol on cardiovascular and neuroendocrine responses to mental arithmetic in type A men.

beta-Adrenergic hyperreactivity has been proposed as a pathogenic mechanism of increased coronary risk in Type A individuals. This study compared the effects of propranolol, diazepam, and placebo on cardiovascular and neuroendocrine responses to a stressful cognitive task in six young Type A males. Although diazepam did not differ from placebo, propranolol attenuated heart rate and norepinephrine responses and enhanced cortisol responses to the task. Findings suggest that propranolol has reciprocal effects on the norepinephrine and cortisol components of the "fight-flight" response. Possible central nervous system mechanisms are described.

Adult↗
PubMed1987

Early ontogeny of kappa-opioid receptor regulation of prolactin secretion in the rat.

Although both mu- and kappa-opioid components of prolactin (PRL) secretion have been identified in the adult rat, the neural pathways through which these multiple receptor subtypes modulate PRL secretion have not been thoroughly investigated. The present study utilizes the differential ontogeny of opioid systems which alter PRL release to examine the mechanisms by which mu- and kappa-receptors regulate prolactin. The responses of PRL, corticosterone and growth hormone to opioid receptor subtype-specific agonists were studied in neonatal rats. The PRL response to the kappa-agonist, U50488, preceded the response to the mu-agonist, morphiceptin. Like adults, neonates demonstrated a growth hormone, but not a PRL, response to the delta agonist, [D-pen2,pen5]enkephalin. U50488-induced PRL secretion was not attenuated by cyproheptadine in adults or neonates, suggesting that the kappa-opioid mechanism operates independently of serotonin. In contrast, the PRL response to morphine was attenuated in adult rats. In addition, U50488 decreased median eminence dopamine synthesis in both adults and neonates. These findings suggest that the early developing, serotonin-independent opioid regulation of PRL is mediated through kappa-receptors, while the later-developing mechanism which requires intact serotonergic transmission works through mu-receptors. kappa-Receptors appear to regulate PRL secretion by directly inhibiting the activity of tuberoinfundibular dopamine neurons, while mu-receptors might regulate the tonic dopaminergic inhibition of PRL through a serotonergic pathway.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
PubMed1987

Exaggerated peripheral responses to catecholamines contributes to stress-induced hyperglycemia in the ob/ob mouse.

The present study investigated the contribution of altered sympathetic reactivity to the stress-induced hyperglycemia observed in the c57BL/6J (ob/ob) mouse, an animal model of type II diabetes. Blood glucose and insulin responses to sympathetic agonist and antagonist administration were evaluated in ob/ob mice and their nondiabetic, lean (ob/?) littermates. In addition, the ability of nutritional status to modify these responses was determined. These studies demonstrated that epinephrine administration to ob/ob mice caused an exaggerated increase in blood glucose and decrease in plasma insulin in ob/ob mice relative to lean littermates. The dose response curve for epinephrine-induced increases in blood glucose were shifted to the left, and the duration of the blood glucose and plasma insulin responses was longer. Differences between ob/ob mice and their nondiabetic littermates were greater when animals were tested in the fasted state. In addition, administration of the alpha adrenergic antagonist phentolamine caused a larger increase in plasma insulin in ob/ob mice than was observed in lean littermates. These results suggest that altered peripheral responses to sympathetic stimuli contribute to stress-induced hyperglycemia in ob/ob mice, and raise the possibility that altered sympathetic function is an etiologic factor in development of diabetes in these animals.

Adrenergic Fibers↗
PubMed1987

Role of serotonin in opiate-induced prolactin secretion and antinociception in the developing rat.

Our laboratory has demonstrated previously that the ability of opiates to stimulate prolactin (PRL) release during ontogeny precedes the appearance of a PRL response to serotonergic drugs. The present study tests the hypothesis that opiates stimulate PRL secretion through a serotonergic mechanism in adult rats, but a nonserotonergic mechanism in neonatal rats. Morphine stimulated PRL secretion in adult and neonatal (10-day-old) rats and this increase was blocked with the opiate antagonist naloxone. Ten-day-old or adult rats were pretreated with the serotonin antagonist, cyproheptadine (CYPRO), or the neurotoxin, 5,7-dihydroxytryptamine (5,7-DHT). Both CYPRO and 5,7-DHT attenuated the PRL response to morphine in adult but not neonatal rats. 5,7-DHT decreased serotonin and 5-hydroxyindoleacetic acid substantially in the hypothalamus. When rats were pretreated with 5,7-DHT several weeks before morphine challenge, serotonin depletion was more pronounced, but the PRL response to morphine was not decreased. In addition, the PRL response to 5-hydroxytryptophan was greatly potentiated, suggesting that functional supersensitivity developed in the 5,7-DHT-treated animals. The ability of CYPRO and 5,7-DHT to block the serotonergic component of a different morphine-induced behavior in the neonate was tested using the tail immersion test for analgesia. Morphine produced profound antinociception in the rat pup which was attenuated markedly by 5,7-DHT and CYPRO. These studies demonstrate that opiates mediate their stimulatory effects on PRL release, at least in part, through a serotonergic mechanism in adult rats.(ABSTRACT TRUNCATED AT 250 WORDS)

5,7-Dihydroxytryptamine↗
PubMed1987

Differential ontogeny of opioid, dopaminergic and serotonergic regulation of prolactin secretion.

The goal of this study was to determine if the opioid system which is stimulatory to prolactin (PRL) secretion develops before the serotonergic system which regulates PRL release. The opioid and serotonergic systems were chosen for comparison because evidence exists that functional serotonergic neurons are necessary for opiate-induced PRL secretion in adult rats. Haloperidol and morphine produced a dose-related stimulation of PRL release in animals of all ages. In contrast, the serotonin agonists, quipazine and m-chlorophenylpiperazine, and the serotonin-releasing drug p-chloroamphetamine produced dose-related increases in PRL release in adult rats, but not in neonatal rats. The PRL response to the serotonin precursor 5-hydroxytryptophan was potentiated by fluoxetine only in animals 15 days of age or older. PRL secretion induced by these serotonergic agents was blocked by cyproheptadine, a serotonin receptor antagonist. Unlike PRL, corticosterone and growth hormone secretion were stimulated by quipazine and 5-hydroxytryptophan plus fluoxetine in both adult and neonatal rats. These findings suggest that stimulatory opioid control of PRL secretion and the dopaminergic mechanism which tonically inhibits PRL release are intact in the neonatal rat. In contrast, the stimulatory serotonergic mechanism is not functional until between 10 to 15 days of age. This late maturation appears to be specific to the serotonergic neurons regulating PRL release because the corticosterone and growth hormone responses to serotonergic stimulation develop early in ontogeny.

5-Hydroxytryptophan↗
PubMed1986

Positive effects of tactile versus kinesthetic or vestibular stimulation on neuroendocrine and ODC activity in maternally-deprived rat pups.

Previous studies in our laboratory have shown that even short-term separation of preweanling rat pups from the mother produces adverse effects in the pup. These include alterations in ornithine decarboxylase activity and in the secretion of growth hormone and corticosterone. The present study demonstrates that while intermittent heavy stroking effectively reverses or prevents all the changes associated with maternal deprivation neither kinesthetic nor vestibular stimulation affects these responses. The results verify earlier findings from this laboratory indicating that tactile interactions between rat pups and their mother modulate pup physiology and provide experimental support for the hypothesized role of tactile stimuli on early infant development.

Animals↗
PubMed1986

Effects of beta-endorphin on ornithine decarboxylase in tissues of developing rats: a potential role for this endogenous neuropeptide in the modulation of tissue growth.

Ornithine decarboxlyase (ODC) catalyzes the initial step in the bio-synthesis of the polyamines spermidine and spermine, which are key regulators of cell growth, proliferation and differentiation. Intracisternal administration of beta-endorphin (1 microgram) to 6 day-old rats markedly decreased brain, liver, heart and kidney ODC activity. Conversely, subcutaneous administration of beta-endorphin increased ODC activity in the heart and liver. Thus, ODC inhibition in peripheral organs in rat pups given beta-endorphin intracisternally appears to reflect central effects of this neuropeptide. Experiments were also carried out to test whether opioid receptors are involved in these tissue ODC responses. Naloxone prevented the decreases in brain ODC indicating the participation of opioid receptors in that process. In contrast, naloxone did not alter ODC responses in peripheral organs in rat pups given beta-endorphin intracisternally, indicating that these effects are independent of its classical opioid character. These results support the view that endogenous beta-endorphin may play an important role in organogenesis by modulating the growth-related enzyme ODC. The data also suggest that the regulation of peripheral organ development by beta-endorphin may be mediated through the release of growth regulatory substances from the CNS.

Animals↗
PubMed1986

Catecholaminergic regulation of opiate-stimulated growth hormone secretion in the developing rat.

In adult rats, the noradrenergic system plays a role in pulsatile and opiate-stimulated growth hormone (GH) secretion through stimulation of alpha-2 adrenergic receptors. The present studies examine catecholaminergic mechanisms which might regulate GH release in the neonatal rat. Catecholaminergic involvement in opiate-induced GH secretion was examined in 10-day-old and 30-day-old rats. Rats were sacrificed 30 min after administration of methadone (2.5 mg/kg s.c.) and serum was analyzed for GH by radioimmunoassay. Reserpine (1 mg/kg s.c.) abolished methadone-induced GH release in neonatal rats. Haloperidol (1 mg/kg s.c.) but not cyproheptadine (5 mg/kg i.p.) attenuated methadone-stimulated GH release. The role of noradrenergic neurons in opiate-induced GH secretion was examined by pretreating rats with diethyldithiocarbamate (400 mg/kg i.p.) or phenoxybenzamine (10 mg/kg i.p.). Both treatments blocked methadone-induced GH release in neonatal rats. In 30-day-old rats, pretreatment with yohimbine (2.5 mg/kg i.p.), but not prazosin (2.5 mg/kg s.c.) blocked opiate-induced GH release. Although selective blockade by these alpha-1 and alpha-2 antagonists could not be demonstrated in neonatal rats, the alpha-2 agonist, clonidine, did stimulate GH release in a dose-related manner. Findings suggest that noradrenergic mechanisms participate in the regulation of GH secretion in both neonatal and adult rats. A tonically active alpha-2 system is demonstrable in neonates despite the absence of GH surges. The GH response to opiates appears to be mediated through this mechanism. Neural regulation of surging may develop as a separate pathway or become superimposed on the neonatal circuit.

Animals↗
PubMed1986

Tactile/kinesthetic stimulation effects on preterm neonates.

Tactile/kinesthetic stimulation was given to 20 preterm neonates (mean gestational age, 31 weeks; mean birth weight, 1,280 g; mean time in neonatal intensive care unit, 20 days) during transitional ("grower") nursery care, and their growth, sleep-wake behavior, and Brazelton scale performance was compared with a group of 20 control neonates. The tactile/kinesthetic stimulation consisted of body stroking and passive movements of the limbs for three, 15-minute periods per day for a 10 days. The stimulated neonates averaged a 47% greater weight gain per day (mean 25 g v 17 g), were more active and alert during sleep/wake behavior observations, and showed more mature habituation, orientation, motor, and range of state behavior on the Brazelton scale than control infants. Finally, their hospital stay was 6 days shorter, yielding a cost savings of approximately $3,000 per infant. These data suggest that tactile/kinesthetic stimulation may be a cost effective way of facilitating growth and behavioral organization even in very small preterm neonates.

Body Weight↗
PubMed1985

Hepatic cyclic AMP generation and ornithine decarboxylase induction by glucagon and beta adrenergic agonists.

The relationship of hepatic ornithine decarboxylase (ODC) activity to cyclic AMP levels and nutritional status was studied in the pre-weanling rat. Previous studies demonstrated that 2 hr without food causes a loss of hepatic ODC induction after glucagon or catecholamine injection. Isoproterenol or glucagon administration produced increased hepatic cyclic AMP and tyrosine aminotransferase activity which were not prevented by nutritional deprivation. Blockade of hepatic beta 2 receptors by the selective antagonist ICI 118,551 prevented increased cAMP levels and ODC activity after isoproterenol administration. Blockade of beta 1 receptors by atenolol did not prevent increased cAMP levels or ODC induction by isoproterenol although it did block activation of cardiac ODC. The phosphodiesterase inhibitor RO20-1724 increased hepatic cAMP levels as well as ODC and TAT activities, although the increase in ODC activity was attenuated by nutritional deprivation. RO20-1724 also potentiated the induction of hepatic ODC after glucagon or isoproterenol administration. Administration of 8-bromo cAMP elevated hepatic ODC activity regardless of nutritional status but also elevated serum levels of growth hormone and corticosterone. Hepatic ODC induction by glucagon or beta 2 agonists can be dissociated from changes in cAMP levels during nutritional deprivation.

4-(3-Butoxy-4-methoxybenzyl)-2-imidazolidinone↗
PubMed1985

Ontogeny of food deprivation effects on ornithine decarboxylase: ornithine decarboxylase induction by alpha and beta agonists.

Short-term food deprivation (FD) of preweanling rat pups causes a marked and specific suppression of liver ornithine decarboxylase (ODC) induction by alpha and beta adrenergic agonists that is mediated by postreceptor mechanisms. In the present study, we demonstrate that FD also affects the ability of adrenergic agonists to induce hepatic ODC in older animals and that these changes differ from those occurring in neonates in the duration of FD associated with changes, the subcellular mechanisms involved and the organ specificity of the effect. FD (48 hr) of 30-day-old rats caused a specific suppression of liver ODC induction by the alpha agonist phenylephrine whereas the effect of the beta agonist isoproterenol was not changed. ODC induction by vasopressin or angiotensin was unaffected, whereas the effect of aminophylline was potentiated. FD of 30-day-old rats caused a marked suppression of both alpha and beta agonist action in the heart. FD of mature (60-day-old) rats was associated with an enhanced hepatic ODC response to phenylephrine and isoproterenol. Whereas the number of receptors in heart assessed by the binding of [3H]prazosin and [125I]pindolol to alpha and beta receptors, respectively, decreased in parallel with changes in responsivity, liver ODC responses did not correlate well with receptor changes. These findings support previous findings of altered sympathetic responsivity in heart, liver and fat during FD and indicate that the sympathetic nervous system responds to FD with a complex series of changes in both pre- and postsynaptic mechanisms.

Adrenergic alpha-Agonists↗