Dissociation of Cyclic GMP Level from Relaxation of the Distal, but Not the Proximal Colon of Rats

Abstract

ABSTRACT-The relevance of endogenously released DOPA to the (±)-nicotine-induced increase in loco motor activities was explored in rats. This increase was dose (0.1-1.0 mg/kg, s.c.)-dependent, stereo selective and mecamylamine (1.0 mg/kg, s.c.)-sensitive, but was not antagonized by L-dopa methyl ester (200 pg, i.v.t.), a competitive L-dopa antagonist. Then, by microdialysis, low doses of a-methyl p-tyrosine (a-MPT, i.p.) at 1-10 mg/kg, were tested to find a dose that selectively inhibits the basal DOPA release in the striata: the release was consistently inhibited by 3 mg/kg without any tendency to inhibit the basal dopa mine release. Pretreatment with this dose did inhibit the nicotine-induced increases in locomotor activities. This suggests that endogenously released DOPA is in part relevant to the nicotine-induced behavior in rats.Keywords: DOPA (endogenous neuroactive substance), Nicotine (increase in locomotor activity), a-Methyl p-tyrosine L-3,4-Dihydroxyphenylalanine (L-dopa) is believed to exert its actions via conversion to dopamine (DA) by L aromatic amino acid decarboxylase (AADC) (1). In con trast to this, we have proposed that DOPA itself is a neu ro-transmitter and/or -modulator in the central nervous system. Depolarizing stimuli released endogenous trans mitter-like DOPA from rat striatal slices (2, 3). A trans mitter-like basal DOPA release was seen under physiologi cal conditions in the striata of conscious rats (4). On the other hand, in in vitro rat brain slices (5 7), exogenous nanomolar L-dopa itself stereo selectively facilitated the evoked release of DA and noradrenaline (NA) via pro pranolol-sensitive presynaptic (3-adrenoceptors even un der complete inhibition of AADC. However, this facilita tion was antagonized competitively by L-dopa methyl es ter, whereas it was noncompetitively antagonized by pro pranolol (7). Then, picomolar L-dopa itself stereoselective ly potentiated the isoproterenol-induced facilitation of the NA release (8). This potentiation was selectively an tagonized by L-dopa methyl ester, whereas propranolol an tagonized both the facilitation by isoproterenol alone and its potentiation by L-dopa. Thus, there exists a recogni tion site for DOPA itself, which differs from presynaptic Nicotine releases various neuro-transmitters or -modu lators in the central and peripheral nervous systems. Peripheral application of nicotine increases locomotor ac tivities of rats (10), and this increase seems to be linked to the DA release (11). On the other hand, local perfusion of nicotine into the rat striatum released transmitter-like DOPA via tonically functioning nicotinic acetylcholine receptors (12). Thus, we have attempted to clarify whether i.v.t.-application of L-dopa methyl ester an tagonizes nicotine-induced increases in locomotor activ ities and then whether endogenously released DOPA is relevant to this behavior in rats.Male Sprague-Dawley rats (300-400 g) were given food pellets and water ad libitum and kept on a regular day and night schedule (lights on at 5:00 hr and off a...

Mechanisms of Meconium Passage: Cholinergic Stimulation of Electromechanical Coordination in the Fetal Colon

“…Recently, we observed that urocortin, a neuropeptide locally expressed in high concentration in the distal colon, exerts a profound inhibitory effect on cholinergic-induced contractility in longitudinal smooth muscle strips of distal colon. 23 The involvement of different inhibitory intracellular signaling mechanisms in mediating proximal and distal colonic smooth muscle relaxation has recently been hypothesized based on results of studies of rat and rabbit smooth muscle preparations. 4 26 Other findings report regional differences in neural number24 and muscle morphology.27 Thus, anatomical differences in neuromuscular apparatus and cell signaling mechanisms may provide a molecular explanation for the observed differences in motor pattern.…”

"Papel da atividade física espontânea no comportamento e na neurotransmissão em áreas do circuito mesocorticolímbico de reforço e do hipocampo em ratos durante a administração crônica de nicotina"

“…A nicotina altera vários tipos de parâmetros comportamentais, incluindo ansiedade, cognição, ingesta alimentar, atividade locomotora (Imperato et al, 1986;Clarke et al, 1988;Di Chiara e Imperato, 1988;Nakamura et al, 1993;Vezina et al, 1994), atenção e memória (Mansvelder et al, 2006) (Everitt et al, 2001). A nicotina pode exercer seus efeitos cognitivos e de atenção (Coull, 1998;Sarter et al, 2001) não somente no Córtex Pré-Frontal (Cabeza e Nyberg, 2000;Rueckert e Grafman, 1996, 1998 como também no hipocampo (Levin, 2002;Newhouse et al, 2004).…”

“…A literatura cita que, animais que receberam doses de nicotina apresentam mudanças em vários parâmetros comportamentais, incluindo atividade motora e escovação do pêlo (grooming) (Imperato et al, 1986;Clarke et al, 1988;Di Chiara e Imperato, 1988;Nakamura et al, 1993;Vezina et al, 1994), e que a exposição crônica a nicotina causa um aumento de longa duração na arborização dendrítica e na densidade dos espinhos dendríticos no Nucleus Accumbens e no Córtex Pré-Frontal (Robinson e Kolb, 2004).…”